Rebels have penetrated the heart of Syria's power elite overnight, detonating a bomb inside a high-level crisis meeting in Damascus that killed three leaders of the regime, including President Bashar Assad's brother-in-law and the defence minister.
The unprecedented blow to the ruling dynasty could mark a turning point in the civil war, suggesting that those once close to Assad are turning against him. The bombing follows some of the worst bloodshed in Damascus of the 16-month uprising, a growing list of high-ranking defections and mounting frustration by world leaders over their inability to find a diplomatic solution.
The White House said the bombing showed Assad was "losing control" of Syria.
Rebels claimed responsibility for the attack, saying they had been planning it for two months and finally decided to plant the bomb in the room where the top government security officials in charge of crushing the revolt were holding a crisis meeting.
"God willing, this is the beginning of the end of the regime," said Riad al-Asaad, a commander of the disparate rebel forces who operate across the country. Al-Asaad, who is not related to the president, spoke to The Associated Press by telephone from Turkey, where he is based.
"Hopefully Bashar will be next," Al-Asaad said in a chilling warning to the 46-year-old Syrian president, a tall, lanky leader who once felt so confident in his security that he was known to hate being surrounded by bodyguards.
The whereabouts of Assad, his wife and his three young children were not immediately clear. He gave no immediate statements on the attack, which state-run TV initially blamed on a suicide bomber but later called simply a bomb.
As news of the assassinations broke, Syrians opposed to Assad celebrated in several locations across the country.
Internet video showed people in convoys of cars and motorbikes honking their horns and firing weapons in the air in the northeastern Idlib province, along with Aleppo in the north, Daraa in the south and Homs in central Syria. In the village of Hass, residents distributed sweets as they gleefully shouted: "You are going to hell, shabihas" - a reference to the pro-regime militia that has been blamed for mass killings.
The AP could not immediately verify the authenticity of the video.
Syrian TV confirmed the deaths of Defence Minister Dawoud Rajha, 65, a former army general and the most senior government official to be killed in the rebels' battle to oust Assad; General Assef Shawkat, 62, the deputy defence minister who is married to Assad's elder sister, Bushra, and is one of the most feared figures in the inner circle; and Hassan Turkmani, 77, a former defence minister who died of his wounds in the hospital.
Also wounded were Interior Minister Mohammed Shaar and Major General Hisham Ikhtiar, who heads the National Security Department. State TV said both were in stable condition.
Rajha was the most senior Christian government official in Syria, appointed to the post by Assad last year. His death will resonate with Syria's Christians, who make up about 10 per cent of the population of 22 million and have mostly stood by the regime.
Christians say they are particularly vulnerable and they fear that Syria will become another Iraq, with Christians caught in the crossfire between rival Muslim groups.
The attack came at a time of great momentum for the forces trying to oust Assad, whose family has ruled Syria for four decades. Although the uprising began in March 2011, recent weeks have seen a spike in potentially transformative events, including high-level defections from the regime.
Four straight days of clashes between rebels and government troops this week in Damascus showed the rebels can now infiltrate the tightly controlled capital. On Tuesday (local time), Israel's military intelligence chief said Assad had diverted his troops away from the Israeli border area toward the center of Syria, reflecting the regime's worsening position.
The state-run news agency, SANA, reported the bombing was aimed at the National Security building, a headquarters for one of Syria's intelligence branches and less than 500 metres from the US Embassy. The embassy has been closed since Washington withdrew its ambassador months ago.
Although there were no statements from Assad, Syrian TV said after the attack that a decree from him named General Fahd Jassem al-Freij as the new defence minister. Al-Freij used to be the army chief of staff.
The attack late last night (NZT) was the most brazen by the rebels. The last major attacks on regime figures and government buildings date back to the early 1980s, when the Syrian Muslim Brotherhood waged a guerrilla war to topple the regime of Assad's father and predecessor, President Hafez Assad.
Hafez Assad himself survived an assassination attempt in 1980 when members of the Muslim Brotherhood threw grenades at him, wounding him in the leg.
Paul Salem, director of the Carnegie Middle East Center in Beirut, said the bombing could usher in the end of the Assad regime.
"I think this type of event has massive impact," he said. "A few weeks ago, we were counting the life span of this regime in months. Now after the last week and today, I think you'd have to say weeks. This is a very fast-moving conflict."
Salem said the key signs that the regime is losing its grip are that the fighting has reached Damascus and that a bomb has been planted inside a top-level meeting.
"This is not something that can go on for months," Salem said. "It changes the timetable."
But there were no signs the regime was willing to back down.
Shortly after the attack, the Syrian army said its forces will continue to fight.
"Whoever thinks that by targeting the country's leaders they will be able to twist Syria's arm is disillusioned because Syria's people, army and leadership are now more determined than ever to fight terrorism ... and cleanse the nation from the armed gangs," the army said.
Eager to show the government is still in control of Damascus, the Interior Ministry took journalists on a tour of its quiet neighbourhoods. But even there, traffic on the streets was thin and almost all shops were closed.
Damascus-based activist Omar al-Dimashki said large numbers of troops and plainclothes police were deployed in the streets after the explosion. Snipers took positions on high buildings in different neighbourhoods, he added.
"It's so empty, it reminds me of when Hafez Assad died in 2000," said a resident of Damascus, who declined to be identified for fear of retribution. "Everyone is really scared of the coming days, especially tonight, with the possibility that the regime will take revenge."
The attack came two days before the start of the Muslim holy month of Ramadan, when observant Muslims abstain from eating, drinking and sex from dawn to dusk. Last year, anti-government protests sharply increased during Ramadan.
"The incident today makes clear that Assad is losing control, that violence is increasing rather than decreasing and that all of our partners internationally need to come together to support a transition," said White House spokesman Jay Carney.
The Obama administration also slapped new financial sanctions on Assad's government.
In a sign of Hezbollah's close ties to Syria, the group's leader, Sheik Hassan Nasrallah, said the bombing victims were "comrades" in the struggle against Israel. He said "the most important rockets" that Hezbollah fired on Israel in the 2006 war came from Syria.
"Israel has every right to be happy," Nasrallah said, saying the opposition to Assad serves Israel's interests. "Israel can be happy because pillars in the Syrian army today were targeted and killed."
Israeli Defence Minister Ehud Barak summoned his top security and intelligence advisers to discuss the situation.
Israel fears that militant groups said to be operating in Syria, including al Qaeda, might try to take advantage of any power vacuum to stage attacks on Israel.
Reacting to the bombing, Russian Foreign Minister Sergey Lavrov accused the West of inciting Syria's opposition.
"Instead of calming the opposition down, some of our partners are inciting it to go on," he was quoted as saying by the RIA Novosti news agency. Supporting the opposition is a "dead-end policy," Lavrov said, "because Assad is not leaving voluntarily."