Syrian Prime Minister Riad Hijab has defected from President Bashar al-Assad's government to join "the revolution", his spokesman says.
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 TV said he had been sacked.
Riad Hijab, who is said to have fled with his family, is a Sunni Muslim from the Deir al-Zour area of eastern Syria which has been caught up in the revolt.
Early reports said Mr Hijab had defected to Jordan, but Jordanian state TV later denied this. By Monday afternoon, Mr Hijab's whereabouts were still unknown.'Freedom and dignity'
Earlier, his spokesman Mohammed el-Etri told al-Jazeera TV that he was in "a safe location".
"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," ran Mr Hijab's statement read by his spokesman.
"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."
Mr el-Etri said the defection had been arranged with the Free Syrian Army months before.
He 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.
Riad Farid Hijab
Born in 1966 in Deir al-Zour, eastern Syria
Married with four children
Holds a PhD in agriculture
Joined the local branch of the Baath Party command in 1998
Named governor of the southern province of Qunaytira in 2008
Transferred to head the Latakia governorate around the time protests were first reported - credited in state media with negotiating an end to a sit-in
Appointed minister of agriculture on 14 April 2011
Mr Hijab is the first Syrian cabinet minister to defect.
The BBC's Jim Muir in neighbouring Lebanon says the defection is a stunning blow to President Assad and a clear sign of the stresses building up within the regime.
In Washington, US National Security Council spokesman Tommy Vietor said the defection was "just the latest indication that Assad has lost control of Syria".
Unconfirmed reports suggested that two other cabinet ministers had also deserted and there were claims that a third, Finance Minister Mohammad Jalilati, had been arrested while trying to flee.
But Syrian state TV said he was still in his office working as usual, and it broadcast what it said was a phone interview with Mr Jalilati categorically denying reports that he had been detained.
Last month, Syria's ambassador to Iraq, Nawaf Fares, deserted to the opposition. Like Mr Hijab, he was also from Deir al-Zour. Brig Gen Manaf Tlas, who was considered close to President Assad, also defected in July.
Thirty other generals have crossed into Turkey so far and Turkish news agency Anatolia reported on Monday that another general had fled with five high-ranking officers and more than 30 soldiers.
Our correspondent said Mr Hijab had been regarded as a Baath party loyalist who was appointed following May general elections which were part of President Assad's reform process.
Syrian state TV said Mr Hijab's deputy, Omar Ghalawanji, would replace him as PM.'Aleppo facing carnage'
Hours earlier, state TV said a bomb had gone off on the third floor of the Syrian state TV and radio building in Damascus, wounding three people.
Footage shows inside the blast-hit state TV building, as Jim Muir reports
A BBC Arabic reporter in the capital said the explosion in Umawiyeen Square had "ripped the floor" but transmission was unaffected.
Pro-government forces have regained control of areas of Damascus seized by rebels in recent weeks but the rebels are continuing to hold out in the second city, Aleppo.
Opposition activists reported an intense bombardment of parts of Aleppo on Monday as 20,000 troops surround the northern city.
A spokeswoman for the exiled opposition Syrian National Council (SNC) told French radio station Europe1 that Aleppo was undoubtedly facing "carnage".
Meanwhile, Iran has strongly denied that 48 Iranians seized by Syrian rebels at the weekend include members of Iran's Revolutionary Guards.
Rebels posted an online video of the Iranians on Sunday, saying they had been seized from a bus in Damascus the day before.
The rebels alleged they were on a reconnaissance mission in the capital.
Tehran, a key ally of President Assad, says they were visiting a renowned Shia pilgrimage site and has appealed to Turkey and Qatar to help secure their release. A rebel commander said their documents were still being checked.