The Syrian prime minister, Riad Hijab, has defected from President Bashar al-Assad's government and fled with his family.
Mr Hijab was appointed less than two months ago and his departure is the highest-profile defection since the uprising began in March 2011.
State-run television is reporting that he has been sacked.
The BBC's correspondent in neighbouring Lebanon says the defection is a stunning blow to Mr Assad and a clear sign of the stresses building up within the regime.
White House spokesperson Jay Carney said it's a sign that Mr Assad's grip on power is loosening.
Early reports said Mr Hijab had defected to Jordan, but Jordanian state TV later denied this. By early Tuesday, his whereabouts were still unknown.
Earlier, his spokesperson, Mohammed el-Etri, had told al-Jazeera TV that he was in "a safe location". Mr el-Etri read a statement by Mr Hijab that began:
"I address you today at this grave hour where the country is living under the brunt of genocide and barbarian brutal killing against unarmed people who are simply demanding freedom and a dignified life.
"Today I declare...that I have defected from the terrorist, murderous regime and [am] joining the holy revolution. And I declare that from today I am a soldier of this holy revolution."
First cabinet minister to defect
Mr el-Etri later told the BBC that the Syrian regime was "now in its last throes" and that it had been dealt "a fatal blow" by Mr Hijab's defection.
"This defection was not a matter of days or weeks," he said. "It was in the pipeline for two continuous months through a trusted cell close to the prime minister made up of rebels and aides."
Mr Hijab - a Sunni Muslim from the Deir al-Zour area of eastern Syria, which has been caught up in the revolt - is the first Syrian cabinet minister to defect.
The BBC's correspondent say he had been regarded as a Baath party loyalist who was appointed following May general elections.
Unconfirmed reports have suggested that two other cabinet ministers have also deserted and there have been claims that a third, finance minister Mohammad Jalilati, was arrested while trying to flee.
But Syrian state TV says Mr Jalilati is still in his office working as usual, and it broadcast what it said was a phone interview with him denying reports that he had been detained.