Prime Minister Wael al-Halqi "is safe and he survived the explosion," reported the official Syrian Arab News Agency. There were unconfirmed reports that the prime minister's bodyguard and several others were killed in the blast.
Footage on state television showed several heavily damaged vehicles and debris scattered along a major street in the Mazzeh district, an upscale neighborhood in western Damascus that is home to many senior officials and diplomats.
The state media reported "casualties and material damage," but there was no official word on how many people were injured or if anyone had been killed.
The attack appeared to be a car bomb, though official accounts did not provide specifics.
Halqi, a senior figure in the governing Baath Party, was appointed prime minister last year after his predecessor, Riad Hijab, defected to the opposition and fled to Jordan.
No one immediately claimed responsibility for the attack. The government blamed "terrorists," its standard term for the armed opposition.
Rebels fighting to oust Assad have regularly deployed car bombs and have been blamed for several such attacks in the capital, including a devastating explosion in February on a busy roadway in central Damascus that killed more than 50 people.
The heavily guarded capital is largely under tight government control. But rebels based in suburbs have shown the ability to set off bombs in the city and shell the capital from positions on the outskirts. The military has thwarted several rebel attempts to storm the city from strongholds east of the capital. In recent days the government has been mounting a major counteroffensive against rebels based outside the capital.
Senior government figures have often been targeted for assassination during the two-year uprising against Assad's rule.
Last summer, four top security officials were killed by what the government called a bomb planted in a security building in the capital. A bombing attack at the Interior Ministry in December reportedly wounded Interior Minister Mohammed al-Shaar.
Special correspondent Nabih Bulos in Amman, Jordan, contributed to this report.
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