BEIRUT, Lebanon — The killing on Wednesday of President Bashar al-Assad’s key security aides in a brazen bombing attack, close to Mr. Assad’s own residence, called into question the ability of a government that depends on an insular group of loyalists to function effectively as it battles a strengthening opposition.
The strike dealt a potent blow to the government, as much for where it took place as for the individuals who were targeted: the very cabinet ministers and intelligence chiefs who have coordinated the government’s iron-fisted approach to the uprising. The defense minister and the president’s brother-in-law were both killed, and others were seriously wounded.
The attack on the leadership’s inner sanctum as fighting raged in sections of the city for the fourth day suggested that the uprising had reached a decisive moment in the overall struggle for Syria. The battle for the capital, the center of Assad family power, appears to have begun. Though there was no indication he was wounded, Mr. Assad stayed out of public view — unusual but not unprecedented in a secretive country where the government has long tried to present an image of quiet control.
In Washington, Defense Secretary Leon E. Panetta said that Syria “is rapidly spinning out of control,” and warned Mr. Assad’s government to safeguard its large stockpile of chemical weapons. “It’s obvious what is happening in Syria is a real escalation,” he said at a joint news conference with the British defense minister, Philip Hammond.
The impact of the day’s events reverberated on multiple levels, piercing the psychological advantage that Mr. Assad’s superior military strength has provided in preserving the loyalty of his forces and frightening much of the public into staying home. With the opposition energized and the government demoralized, analysts wondered if other military units and trusted lieutenants would be more inclined to switch sides — and if the government would retaliate with an escalation of violence.
The idea that a poorly organized, lightly armed opposition force could somehow get so close to the seat of power raised questions about the viability of a once unassailable police state. The Assad family has for decades relied on overlapping security forces and secret police to preserve its lock on power. At best, for Mr. Assad, the system failed. At worst, for Mr. Assad, defectors or turncoats helped carry out an inside operation.
The government said that the attack was the work of a suicide bomber, while an officer with the Free Syrian Army said it was a remotely detonated explosive.
The most significant victim was Asef Shawkat — the husband of the president’s older sister, Bushra — who was the deputy chief of staff of the military after years as a top intelligence official. The others killed were Gen. Dawoud A. Rajha, the defense minister and the most prominent Christian in the government; and Maj. Gen. Hassan Turkmani, a previous defense minister serving as the top military aide to Vice President Farouk al-Sharaa.
“Who will replace these people?” asked Elias Hanna, a retired Lebanese military officer and a military analyst knowledgeable about Syria. “They are irreplaceable at this stage; it’s hard to find loyal people now that doubt is sown everywhere. Whoever can get to Asef Shawkat can get to Assad.”
“Everyone, even those close to the inner circle, will now be under suspicion,” he said.
State television also said the minister of the interior, Lt. Gen. Mohamed al-Sha’ar, had been gravely wounded but was in stable condition. Hisham Ikhtiar, the head of general security, was reported by some activist organizations among those in critical condition, along with some junior officers, but the official news media did not confirm that.
The bombing took place in a small, nondescript building in a neighborhood that is home to the country’s elite. The building housed a research center run by the national security agency, one of many overlapping intelligence agencies.
“It was at the heart of the government’s nexus of control,” said an analyst with long experience in Damascus, speaking anonymously because he still travels there often. “If the regime had a center, that was it.”
But the government mounted a show of normality. It quickly appointed a new defense minister, Gen. Fahd Jassem al-Freij, the military chief of staff who had previously been responsible for trying to squash the uprising in northern Idlib Province. He appeared briefly on television, vowing that the military would not be deterred by the attack from “cutting off every hand that harms the security of the homeland and citizens.”
The military also issued a statement saying in part, “This terrorist act will only increase our insistence to purge this country from the criminal terrorist thugs and to protect the dignity of Syria and its sovereignty.”
Activists reported an even harsher crackdown, with government soldiers firing indiscriminately in several embattled neighborhoods or from helicopters, especially on the southern part of Damascus where fighting first erupted Sunday. Dozens of people were killed, and defections soared, activists said.
“The regime reacted hysterically to the attack,” said Rami al-Sayyed, an activist in Damascus. “The security forces and thugs infiltrated various neighborhoods, committing all kinds of crimes. Today we cut the head of the snake, but we still have the tail.”
Like any event in Damascus, details surrounding the attack were murky. There were competing accounts of how the attack occurred and competing claims of responsibility. The Free Syrian Army based in Turkey said it had helped carry out the attack. Also, a brigade from a group with a seemingly religious bent called the Islamic Battalions said it was responsible.
Lt. Malik al-Kurdi, the second in command of the Free Syrian Army troops in Turkey, said it was not a suicide bombing but “bombs planted around the national security building” that were set off by remote control.
Since the uprising began in March 2011, claiming an estimated 17,000 victims, Syria has been run by an ever tighter circle of army and security officials close to the president. General Rajha was one of the prominent minority figures used by the Assad government to put a face of pluralism on the military and security services dominated by the president’s Alawite sect.
“The Syrian regime has started to collapse,” said the activist who leads the Syrian Observatory, who goes by the pseudonym Rami Abdul-Rahman for reasons of personal safety. The attack heightened the perception globally that after months of clashes, Syria was embroiled in a civil war.
On the other end of the scale, Hassan Nasrallah, the leader of Hezbollah, delivered an emotional speech live on television, saying that the Syria of Mr. Assad and Mr. Shawkat was the backbone of the Arab confrontation with Israel.
The attack came as diplomatic maneuvers to seek a cease-fire remained deadlocked by differences between Syria’s international adversaries and sponsors, principally Russia. The United Nations Security Council is scheduled to vote on a Western-sponsored resolution that would threaten Mr. Assad’s government with economic sanctions if it does not implement a peace plan negotiated by the special envoy Kofi Annan more than three months ago.
The resolution, which Russia has threatened to veto, would extend the mission of 300 unarmed United Nations monitors, whose work has been suspended because of the violence.
Security Council members agreed to delay the vote, originally scheduled for Wednesday, until Thursday at Mr. Annan’s request, to allow more time for diplomats to resolve their differences over the resolution’s wording.
But in Moscow, Deputy Foreign Minister Gennady Gatilov, offering Russia’s first official commentary on the Damascus bombing, said via his Twitter account that the attack had put consensus between members of the Security Council even further out of reach.
“A dangerous logic: While discussions on settling the Syrian crisis are being held in the U.N. Security Council, militants intensify terrorist attacks, frustrating all attempts,” he wrote.
In Syria, the information minister, Omran al-Zoubi, appeared on a talk show to reject claims by those calling it the beginning of the end.
“The morale of our people is very high and our armed forces are at their highest level,” he said.
But residents of Damascus had been shaken as never before. Residents reached by telephone said that after the news broke around noon, people rushed out to buy food and then rushed back home again. City streets appeared deserted, with not even taxis circulating after dark.
“All the stores and shops are closed,” said an activist in Damascus reached via Skype. “Some people are scared and some are happy; you can hear people firing off gunshots in many places.” A video from Hama showed opposition members distributing candy to celebrate Mr. Shawkat’s death.
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