The Taftanaz air base in the northern Idlib province is considered the biggest field in the country's north for helicopters used to bomb rebel-held areas and deliver supplies to government troops.
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"With Allah's help, we are headed in your direction, Bashar," the rebels said in a statement published on rebel-affiliated websites, which celebrated the takeover.
"We should enjoy this victory," one website wrote. "A first airport has fallen in the hands of rebels of the Jabhat al-Nusra Jihad fighters."
Another website said, "We bring you the good news of the liberation of the military airport of Taftanaz and its complete purification. This airport is the biggest helicopter base in northern Syria and the second biggest in all of Syria, and is the gate for the liberation of the Idlib province with the help of Allah."
Rebels from the al-Qaeda affiliated Jabhat al-Nusra and other Islamic groups have been fighting for weeks for control of the sprawling facility and broke into it on Wednesday evening. Activists said the rebels seized control of buildings, ammunition and military equipment after ferocious fighting at dawn.
"As of now, the rebels are in full control of the air base," said Idlib-based activist Mohammad Kanaan.
Syrian Observatory for Human Rights director Rami Abdel Rahman said it was the first major military airport to fall into rebel hands. He said warplanes bombed it after the rebel takeover.
"The fighting at Taftanaz military airport ended at 11 am and the base is entirely in rebel hands," he said.
Soon afterwards, it was raided by government jets, the Britain-based Observatory said.
"Warplanes are bombing Taftanaz military airport in an attempt to destroy it," a statement said.
Syria talks end in Geneva without solution
The news came as UN-Arab League special envoy on Syria Lakhdar Brahimi met Russian Deputy Foreign Minister Mikhail Bogdanov and US Undersecretary of State William Burns in Geneva.
Brahimi said that Russia seemed as determined as the United States to end Syria's civil war, but that he didn't expect a political solution to emerge anytime soon.
"We are all very, very deeply aware of the immense suffering of the Syrian people, which has gone for far too long. We all stressed the need for a speedy end to the bloodshed, to the destruction and all forms of violence in Syria. We stressed again that in our view, there was no military solution to this conflict," Brahimi told reporters.
But he acknowledged that "if you are asking me whether a solution is around the corner, I am not sure that is the case. What I am certain of is that there is an absolute necessity for people to continue to work for such a peaceful solution, and that it is the wider international community, especially members of the Security Council, that can really create the opening that is necessary to start effectively solving the problem."
Brahimi's five hours of talks with Bogdanov and Burns on Friday ended without any apparent deal. It was Brahimi's second meeting in as many months with Bogdanov and Burns, who each left without making any public comments.
In December, Brahimi also met with Russian Foreign Minister Sergey Lavrov and US Secretary of State Hillary Rodham Clinton to discuss Syria.
Also on Friday, Arab media outlets reported that a car bomb exploded al-Tura Street in the Damascus.
Overnight opposition sources claimed Assad's army massacred more than 50 people in the Al-Houl region in Al-Hasakah District, located in Syria's northeast. The sources said most of the victims were women and children who were killed in aerial bombings and by artillery fire.
AFP contributed to this report