The United States Secretary of State said Syrian President Bashar al-Assad has “lost legitimacy”, amid diplomatic tension between the two countries.
Speaking after a crowd attacked the United States embassy in Damascus, Hillary Clinton said Mr Bashar was “not indispensable”.
France blamed the regime after its embassy was similarly targeted.
The embassy attacks came after the American and French envoys visited the troubled city of Hama last week, drawing sharp criticism from Syrian media.
Pro-government demonstrators had been taking part in protests outside both embassies for the past two days.
An embassy official told the BBC the compound had been assaulted by a “mob”, but that no-one had been hurt.
The residence of the ambassador, Robert Ford, was later briefly attacked, the state department said.
In Washington, Mrs Clinton demanded that the Syrians “meet their international responsibilities immediately to protect all diplomats and the property of all countries”.
She added: “President Assad is not indispensable and we have absolutely nothing invested in him remaining in power.
“Our goal is to see that the will of the Syrian people for a democratic transformation occurs.”
The BBC’s Kim Ghattas in Washington said her statement was cleverly worded – it might convince more Syrians to give up on Mr Assad, while not requiring any action by Washington which can continue to say it is up to the Syrian people to chose their leaders.
Our correspondent added that the US had been wary of a repeat of the Libya scenario, where after calling for Col Muammar Gaddafi to leave power, it struggled to make that happen.
State department spokeswoman Victoria Nuland said a Syrian diplomat would be summoned over attack on the embassy, and compensation for the damage would be demanded. (BBC)
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