A rebel suicide bombing of Syria's security headquarters has killed President Bashar al-Assad's brother in law Assef Shawkat and the defense minister Daoud Rajiha, according to reports.
The interior minister and the intelligence chief, Hisham Bekhityar, were reportedly wounded in Wednesday's attack, Lebanese Hezbollah TV claimed.
The bombing is the latest attack by rebels as they carry out Operation Volcano - an all-out assault on the Assad regime in Damascus.
A barracks overlooking the presidential palace was said to be ablaze, while earlier there were reports of gunfire and plumes of smoke coming from near the parliament building, according to the BBC.
Rajiha was a Christian and according to experts his death might increase Christian support for Assad's regime.
Fighting in the city between government forces and rebels has entered its fourth day, forcing the regime to deploy tanks and helicopter gunships in Damascus for the first time.
On Tuesday, Sky news reported rebels had managed to down a helicopter. A senior rebel told the broadcaster: Helicopters are flying at low altitude. It's easy to target them using anti-aircraft weapons.
Following Wednesday's bombing, Republican guard troops surrounded Shami hospital in Damascus after ambulances brought casualties from the explosion site.
A suicide attack has targeted the National Security building, Syrian state TV said. 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.
A number of Syrian officials were said to be badly wounded, according to the BBC, which confirmed the death of Rajiha.
The battle for the liberation of Damascus has begun, Colonel Qassim Saad Eddine, a Homs-based member of the Free Syrian Army, told Lebanese TV, according to the Los Angeles Times.
We have a clear plan to control the whole of Damascus. We have only light weapons, but it's enough.
The joint commander of the Free Syrian Army said a military operation dubbed Damascus Volcano - Sham Cataclysm had been launched to bring down the regime of Assad.
Syrian officials have denied claims of an all-out rebel offensive.
Meanwhile, reports Syria has started moving some of its huge stockpile of chemical weapons out of storage have alarmed international observers.
Nawaf Fares, the former Syrian ambassador to Iraq and the most senior Syrian official to defect to the opposition, has said that the Syrian regime will not hesitate to use chemical weapons in a last-ditch effort at survival.