A suicide bomber killed three of Syrian President Bashar al-Assad's top military officials on Wednesday, security sources said, the worst blow to Assad's high command in the country's 16-month-old rebellion.
The bomb killed Assad's powerful brother-in-law, the defense minister and a top general, bringing the battle to the heart of Assad's powerbase and sparking fighting across Damascus.
Residents, fearing fierce retaliation by Assad's forces, said army helicopters fired machineguns and in some cases rockets at several residential districts. Television footage showed rebels storming a security base in southern Damascus.
The bomber, said by a security source to be a bodyguard assigned to Assad's inner circle, struck a meeting in central Damascus attended by ministers and senior security officials as battles raged within sight of the nearby presidential palace.
Washington, which fears a spillover into neighboring states, said the situation seemed to be spinning out of control. Russian Foreign Minister Sergei Lavrov said "the battle for the capital, the decisive fight" was under way. The U.N. Security Council put off a scheduled vote on a Syria resolution.
State television said Defense Minister Daoud Rajha and Assad's brother-in-law Assef Shawkat, the deputy defense minister, had been killed in a "terrorist bombing" and pledged to wipe out the "criminal gangs" responsible.
It said General Hassan Turkmani, a former defense minister and senior military official, had died later of his wounds. Intelligence chief Hisham Bekhtyar and Interior Minister Mohammad Ibrahim al-Shaar were wounded but were "stable".
The men form the core of a military crisis unit led by Assad to take charge of crushing the revolt which grew out of a popular protests inspired by Arab Spring uprisings that unseated leaders in Tunisia, Egypt and Libya.
"I heard...a loud explosion but it was not a very big bang. I went down to take a look and I saw a lot of men in plain clothes with rifles," one resident near the scene told Reuters by telephone. She said windows on the third floor of the national security building were shattered.
Assad did not appear in public in the hours after the attack or make any statement, but security sources said he was not at the meeting where it took place.
The armed forces chief of staff, Fahad Jassim al-Freij, quickly took over as defense minister to avoid giving any impression of official paralysis.
"This cowardly terrorist act will not deter our men in the armed forces from continuing their sacred mission of pursuing the remnants of these armed terrorist criminal gangs," Freij said on state television. "They will cut off every hand that tries to hurt the security of the nation or its citizens."
The explosion appeared to be part of a coordinated assault on the fourth day of fighting in the capital that rebel fighters have called the "liberation of Damascus" after months of clashes which activists say have killed more than 17,000 people.
It began early on Wednesday with fighting around an army barracks in the district of Dummar, hundreds of meters from the presidential palace, and was followed by blasts close to the base of the elite 4th armored division in the southwest. The unit, led by Assad's brother Maher, has been instrumental in crushing protests around Syria.
"This is a situation that is rapidly spinning out of control," U.S. Defense Secretary Leon Panetta said, calling for maximum global pressure on Assad to step down.
Panetta said Assad's government would be held responsible if it failed to safeguard its chemical weapons, which Western and Israeli official have said have been moved from storage sites.
A video posted by activists who said it was filmed in the southern Qadam district showed at least two bodies lying in pools of blood and one rebel commander said at least 45 civilians had been killed in Damascus on Wednesday.
He did not give a figure for rebel or army casualties. The figure could not be confirmed. The Syrian government restricts access by international journalists.
Western leaders fear the conflict, which has been joined by al Qaeda-style Jihadists, could destabilize Syria's neighbors - Israel, Lebanon, Turkey, Iraq and Jordan.
Syrian Information Minister Omran Zoabi blamed Western and Sunni Arab governments for the crisis. "They are responsible for every drop of blood. And they will be accountable," he said.
"I stress to them that this is the decisive battle in all of Syria," Zoabi said on state television.
Rebels say they have brought reinforcements from outside the city to end four decades of rule by the Assad family by attacking the power base of the ruling elite for the first time.
Syrian forces hit rebel positions across the capital after the attack on the security meeting, with activists saying government troops and pro-government militia were flooding in.
State television broadcast footage it said was filmed on Wednesday showing men in blue army fatigues ducking for cover and firing - the first time official media has shown clashes in the heart of the capital.
Two rebel groups claimed responsibility for the attack on the security meeting.
"This is the volcano we talked about, we have just started," said Qassim Saadedine, a spokesman for the Free Syrian Army, a group made up of army defectors and Sunni youths.
Liwa al-Islam, an Islamist rebel group the name of which means "The Brigade of Islam", said it had carried out the attack after weeks of planning and gave a different version of events.
"Our men managed to plant improvised explosives in the building for the meeting. We had been planning this for over a month," a spokesman for the group, who asked to be identified as Abu Ammar, said by telephone. State television said earlier that it was a suicide bombing.
"The terrorist explosion which targeted the national security building in Damascus occurred during a meeting of ministers and a number of heads of (security) agencies," it said.
Fighting also erupted overnight in the southern neighborhoods of Asali and Qadam, and in Hajar al-Aswad and Tadamon - poor, mainly Sunni Muslim districts housing Damascenes and Palestinian refugees.
Assad and the ruling elite belong to the minority Alawite sect, an offshoot of Shi'ite Islam that has held power in Syria since a 1963 coup.
The elite has endured more than a year of rebellion but recent high level defections signaled support beginning to fall away.
Two Syrian brigadier-generals were among 600 Syrians who fled from Syria to Turkey overnight, a Turkish official said on Wednesday, bringing the number of Syrian generals sheltering in Turkey to at least 20.
In Damascus, 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 headquarters for pro-Assad militia, known as shabbiha, drawn mainly from Alawite enclaves in nearby hills.
Rebel fighters have called the intensified guerrilla 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".
Still, opposition figures did not predict sudden victory.
"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."