Syrian Defense Minister General Daoud Rajiha was killed on Wednesday after a suicide bomber struck a government building. Al Jazeera reported that the interior minister and intelligence chief were also injured in the blast.
Wednesday's attack struck the National Security building in Damascus during a meeting of cabinet ministers and senior security officials.
The capital has seen four straight days of clashes pitting government troops against rebels, who are trying to bring down the regime by force.
The fighting is an unprecedented challenge to government rule in President Bashar al-Assad's seat of power.
Al-Manar, a Lebanese-based TV station controlled by Hezbollah reported Wednesday that the Syrian president's brother in-law and Deputy Defense Minister Assef Shawkat was also seriously wounded in the explosion. Sky News reported that Shawkat had actually been killed.
Al-Mayadeen, a Lebanon-based news channel, said several senior security officials had been killed in the blast, without giving details.
Activists in Damascus said by telephone that Republican Guards sealed of the Shami hospital in the capital after ambulances had brought casualties from the site of the explosion.
Earlier Wednesday, an army barracks near the "palace of the people", a huge Soviet style complex overlooking the sprawling capital from the western district of Dummar, came under rebel fire at around 7.30 a.m. (0430 GMT), activists and a resident said.
"I could hear the sound of small arms fire and explosions are getting louder and louder from the direction of the barracks," Yasmine, who works as an architect, said by phone from Dummar.
Video footage broadcast by activists purportedly showed fire in the barracks overnight as a result of an attack by mortar rounds, but residents who saw the fire said they had not heard explosions to indicate it was a result of an attack.
Dummar is a secure area containing many auxiliary installations for the presidential palace and the barracks is just hundreds of meters from the palace itself.
Fighting also erupted overnight in the southern neighborhoods of Asali and Qadam, and Hajar al-Aswad and Tadamun - mainly Sunni Muslim districts housing Damascenes and Palestinian refugees.
Asad and the ruling elite belong to the minority Alawite sect, an offshoot of Shi'ite Islam that has dominated power in Syria since a 1963 coup.
Government troops used heavy machine guns and anti-aircraft guns against rebels moving deep in residential neighborhoods, armed mostly with small arms and rocket propelled grenades.
Rebels directed their fire overnight at a large state facility turned headquarters for pro-Assad militia, known as shabiha, drawn mainly from Alawite enclaves in nearby hills.
Army tanks and anti-aircraft guns, used as an infantry weapon, took positions in the northern neighborhood of Barzeh, where hundreds of families from the neighboring district of Qaboun are seeking shelter.
"Anti-aircraft guns are firing at Qaboun from Barzeh. There are lots of families in the streets with no place to stay. They came from Qaboun and from the outskirts of Barzeh," said Bassem, one of the activists, speaking by phone from Barzeh.
In the central neighborhood of Midan tanks and infantry fighting vehicles known as BDMs took positions in main thoroughfares and sporadic fighting was reported.
"Armor have not been able to enter the alleyways and old streets of Midan. The neighborhoods old Zahra and the old area near Majed mosque are in the hands of the rebels," said Abu Mazen, an activist in the district.
Rebel fighters have called the intensified guerilla attacks in recent days, which have targeted shabbiha buses, unmarked intelligence patrols and armored vehicles in the capital, the battle "for the liberation of Damascus" after 16 months of revolt.
But senior opposition figures took a more nuanced view.
"It is going to be difficult to sustain supply lines and the rebels may have to make a tactical withdrawal at one point, like they did in other cities," veteran opposition activist Fawaz Tello said from Istanbul.
"But what is clear is that Damascus has joined the revolt," Tello, a Damascene, told Reuters. "By hitting well known Sunni districts of the city, such as Midan, the regime is exposing the sectarian nature of the crackdown."
Information Minister Omran Zoabi said on Tuesday security forces were fighting armed infiltrators in Damascus. He said many had surrendered while others "escaped on foot and by car and are firing randomly in the air to frighten people".
16 months ago. Activists say Syrian government forces have also used helicopter gunships to battle rebels in the capital Damascus.
The activists say that helicopters fired heavy machine guns during overnight clashes in the neighborhoods of Qadam and Hajar al-Aswad as a ring of fierce clashes nearly encircled the heavily guarded capital.
Defense Minister Ehud Barak said Monday that, "The fate of the Assad family is sealed, but on its way out of power it can kill more people. The Assad family is holding on to power at the cost of the continued slaughter of its own people. The world understands, the International Red Cross made a very important declaration [on Sunday] that it sees the situation in Syria as a civil war."
Barak added that "there is a disturbing lesson in the fact that the entire world, even when these grave events unfold before all of our eyes, cannot manage to gather the fortitude, legitimacy or the unity required to… put an end to this bloodbath."
Nawaf Fares, Syria's ex-ambassador to Iraq and the most senior Syrian politician to defect to the opposition, told the BBC on Tuesday that Assad's regime will not hesitate to use chemical weapons if it is cornered. When asked if he thought Assad might use chemical weapons against the opposition, Fares replied he could not rule it out, describing Assad as "a wounded wolf and cornered."
"There is information, unconfirmed information of course, that chemical weapons have been used partially in the city of Homs," Fares told the BBC. "It doesn't occur to any Syrian, not only me, that Bashar al-Assad will let go of power through political interventions. ... He will be ousted only by force," he said.
While the clashes in Damascus were focused in a string of neighborhoods in the city's southwest, for many of its four million people the violence brought ominously close to home the strife that has deeply scarred other Syrian cities.
In high-end downtown cafes frequented by the business and government elite tightly bound to the Assad regime, customers watched as black smoke billowed on the horizon and the boom of government shells reverberated in the distance.
"Without a doubt, this is all anyone is talking about today," a Damascus activist who gave his name as Noor Bitar said via Skype. "The sounds of war are clear throughout the city. They are bouncing off the buildings."
Meanwhile, Syrian Ambassador to Belarus Farouk Taha defected on Monday and aligned himself with the rebels. Also Monday, Morocco asked the Syrian ambassador to leave the country. Within hours, Syria's state-run TV said the Foreign Ministry had declared Morocco's ambassador to Syria persona non grata.
International diplomacy has failed to stop the violence, and world powers remain deeply divided over who is responsible and how to stop it. The U.S. and many Western nations have called on Assad to leave power, while Russia, China and Iran have stood by the regime.
Also on Monday, Russian Foreign Minister Sergey Lavrov accused the West of using blackmail to secure a U.N. Security Council resolution that could allow the use of force in Syria. Lavrov objected to the text of a Western-backed resolution that calls for sanctions and invokes Chapter 7 of the U.N. Charter, which can be enforceable militarily. He said Russia had been told that if it opposed the resolution, Western nations would not extend the mandate of a U.N. mission sent to Syria to monitor a cease-fire.
"We consider it to be an absolutely counterproductive and dangerous approach, since it is unacceptable to use monitors as bargaining chips," Lavrov said.
International envoy Kofi Annan, who has made little progress in brokering a political solution in Syria, met Russian leaders in Moscow on Monday. The meeting — the latest in Annan's efforts to save his faltering peace plan — comes a day after the conflict crossed an important symbolic threshold, with the international Red Cross formally declaring it a civil war, a status with implications for potential war crime prosecutions.
Monday's fighting and Wednesday's attack that killed the top minister suggest that deep cracks were appearing in the tightly controlled facade of calm that has insulated Damascus from violence throughout the uprising. Damascus — and Syria's largest city, Aleppo — are both home to elites who have benefited from close ties to Assad's regime, as well as merchant classes and minority groups who worry their status will suffer if Assad falls.
But for months, rebels have been gaining strength in poorer towns and cities in the Damascus countryside. Some activists suggested Monday that recent government crackdowns in those areas had pushed rebels into the city, where they were determined to strike at the heart of the regime.
"It seems there is a new strategy to bring the fighting into the center of the capital," said activist Mustafa Osso. "The capital used to be safe. This will trouble the regime."
Another activist, who gave only his first name, Moaz, said he had never seen such violent fighting in his neighborhood of Tadamon, a poor, densely populated area south of downtown.
He said the army had parked armored vehicles at the neighborhood's entrances and posted tanks on its north and south edges.
Some two-thirds of the neighborhood's residents have fled, while those who remain are scared government snipers will target them if they leave now, he said.
But so far, the rebels have kept the army out, destroying three tanks and one armored car with rocket-propelled grenades, said Moaz, declining to give his full name for fear of retribution. Others spoke on condition anonymity.
Amateur videos posted online Monday gave glimpses of the fighting. In one, a dozen fighters crouched Sunday behind sandbags, firing at a tank down a rubble-strewn street with a machine gun and rocket-propelled grenades. Another video showed a burnt station wagon with at least three charred bodies inside that an off-camera narrator said were government troops.
The fiercest fighting was in the southwest neighborhoods of Mezzeh, Kafr Sousa, Al-Midan, Tadamon, Nahr Aisha and Al-Zahira, while activists also reported clashes in the western suburbs and in the northern neighborhood of Barzeh.
The Britain-based Syrian Observatory for Human Rights said 12 people were killed in and around Damascus, among some 90 people killed nationwide. About a third of the dead were government troops, it said.
Activist claims and videos could not be independently verified. The Syrian government bars most media from working in the country.
The government said little about the clashes, but the state news agency said the army was hunting an "armed terrorist group" in one of the neighborhoods. The regime blames the uprising on terrorists acting out a foreign conspiracy to weaken the country.
Streets were largely deserted in neighborhoods near the fighting. Many families have fled or are still trying to get out, and fear grips those who remain.
"Assad will only go after he kills all of us," said a 28-year-old mother of two reached by phone in the Midan neighborhood, who declined to give her name for fear of reprisals from Syrian security.
The Syrian regime has grown increasingly isolated throughout the crisis, with a number of Arab and Western nations withdrawing their ambassadors to protest the crackdown.
U.S. Ambassador Susan Rice told reporters at U.N. headquarters in New York that Annan should tell the Russians what he told council members last week: "that he needs the council to come together around a resolution that makes very clear that there are consequences for non-compliance."
The British draft circulated Monday among Security Council members threatens non-military sanctions against Assad's government if it doesn't withdraw troops and heavy weapons from population centers within 10 days.
A closed council session Monday afternoon made no progress in bridging the differences.
Rice, the U.S. envoy, said the observer mission has been unable to do its job because of the escalating violence and if the council is not prepared "to back up the mandate we gave them with the tools at our disposal, even to threaten sanctions, not even impose sanctions under Chapter 7, then we're leaving these guys hanging — and it's completely, not only ineffective, but it's immoral."
The Security Council has scheduled a vote on the resolution Wednesday — leaving two days for possible last-minute maneuvering before the observer mission's mandate expires. Both the British and Russian texts have been put in a final form for a vote.
Meanwhile, Lebanese media outlets reported Monday that both the Syrian and Lebanese armies have reinforced their respective armies positioned along their shared border, not only to prevent the civil war in Syria from spilling into Lebanon, but out of concern that Israel may be looking to pre-emptively attack in Syria in order to thwart the transfer of chemical weapons from the Syrian regime to the Lebanon-based Hezbollah terrorist organization.
Assad will now find it more difficult to project business as usual after the rebellion against his regime turned into pitched battles on the streets of the capital Damascus on Monday, and the noose of international pressure around the regime further tightened.