It is "a matter of time" before the Syrian regime headed by President Bashar al-Assad is ousted from power by a popular uprising, US Defence Secretary Leon Panetta said on Monday.
Speaking in Tel Aviv after meeting his Israeli counterpart, Panetta said Washington and other foreign capitals had "made clear Assad should step down."
"While he continues to resist, I think it's very clear that it's a matter of time before that (exit) in fact happens. When it does, we don't know," he said.
The Pentagon chief, in a visit to Israel and the Palestinian territories on Monday, said Assad's regime had lost all credibility after a brutal crackdown that has killed at least 2,700 people, according to the United Nations.
"Anytime you kill your own people as indiscriminately as they have over these last number of months, it's pretty clear that they have lost their legitimacy as a government," Panetta said at a news conference with Israeli Defence Minister Ehud Barak.
Panetta, who served as CIA director until he took over as defence chief in July, pledged the United States and other countries would keep up pressure on the regime to make way for a government more responsive to the needs of its people.
Barak also said the regime's days were numbered and that Assad's fall from power would represent a "major blow" to what he called a "radical axis" of militants in the region supported by Iran.
According to US media reports, American officials are increasingly convinced that Assad's regime will not survive and are bracing for a possibly violent aftermath.
The New York Times has reported that Washington was quietly working with Ankara to plan for a post-Assad scenario that could see Syria's various ethnic groups battle for control of the country.
Despite calling on Assad to step down, the United States has yet to withdraw its ambassador, Robert Ford, instead using him as a conduit to the opposition and Syria's disparate ethnic and religious groups.
Last Thursday, a crowd of nearly 100 Syrians chanting hostile slogans tried to storm an office in Damascus where Ford had arrived to meet opposition figure Hassan Abdelazim, officials said.
In response, the US government summoned Syrian ambassador Imad Mustapha to the State Department last week and "read the riot act" to him over the incident, a spokeswoman said.
Since mid-March, Syria has been shaken by an unprecedented pro-democracy protest movement that the Assad regime has sought to crush using deadly force.
More than 2,700 people have been killed in the unrest, according to the UN High Commissioner for Human Rights in Geneva.
Late Sunday, protesters poured onto the streets in a mass show of support for a powerful opposition grouping that was launched in Istanbul, activists said.
The Syrian National Council drew "demonstrations of support" in the country's main protest hubs, including Hama, Homs, Idlib, Daraa, Deir Ezzor and the province of Damas, according to the Britain-based Syrian Observatory for Human Rights.
The group also said the Syrian army had Sunday "taken complete control" of the central city of Rastan in Homs province, 160 kilometres (100 miles) north of Damascus, where fighting had raged between army deserters and Syrian forces.