Syria's mainstream rebels risk total collapse after a Russian-backed regime advance that severed their main supply line to Aleppo city and threatens to leave them completely besieged there.
Analysts said rebels and their international backers were left with few options to prevent fresh government advances, which came as fresh peace talks backed by the United Nations fell apart.
"The trajectory for the rebels is downwards, and the downward slope is increasingly steep," said Emile Hokayem, senior fellow at the International Institute for Strategic Studies.
Aleppo province was once a rebel stronghold, providing easy access to neighbouring Turkey, a key opposition backer.
The city itself has been divided between rebel control in the east and government control in the west since mid-2012.
But government forces have steadily chipped away at rebel-held territory around the city, and their advances this week leave the opposition there virtually surrounded.
"It is a turning point in the war," said Fabrice Balanche, a visiting fellow at the Washington Institute think tank.
"The opposition wanted to make Aleppo and (neighbouring) Idlib province the base of a 'free Syria'. That's over."
The advance is the most significant outcome yet of the Russian intervention that began on September 30, ostensibly targeting the Islamic State group and other "terrorists".
Analysts and activists say Russia's strikes have always disproportionately targeted non-Islamist militant rebels in an attempt to bolster President Bashar al-Assad's government.
"Aleppo is simply the first dramatic display of how the combination of Russian air power and advisers has been able to make up for the regime's relatively low capabilities and manpower shortage," said Faysal Itani, a senior fellow at the Atlantic Council's Rafik Hariri Centre for the Middle East.
Opposition forces and some 350,000 civilians inside rebel-held Aleppo city now face the prospect of a government siege, a tactic that has been employed to devastating effect against other former rebel strongholds such as Homs.
"A good deal of both (rebels and civilians) will die from bombardment, starvation and the general deprivations of siege," said Itani.
"The fighters inside will be killed or forced to surrender," he added, predicting fresh waves of refugees.
There was already evidence of a new unfolding humanitarian disaster, with tens of thousands of people reportedly fleeing the government advance and massing on the border with Turkey seeking entry.
More than 260,000 people have been killed in Syria's conflict since March 2011, with half the country's population displaced internally or abroad.
Activists said the opposition felt betrayed, reporting that weapon supplies from international backers had dried up in advance of the Geneva peace talks, despite stepped-up Russia military action.
"What frustrates the rebels the most is that the countries that claim to be their friends are happy with empty words and sitting on the fence," said activist Maamoun al-Khatib, head of the Shabha press agency in Aleppo.
"Meanwhile Russia and Iran are occupying and violating Syrian territory."
Experts said the rebels had few options left.
"There is not much manpower to spare as other rebel areas are also under pressure and this would not address the issue of enemy air power," said Itani.
Syria's rebels have long sought anti-aircraft weaponry from international backers, but Washington has held back for fear they would end up in the hands of Islamist militans such as Al-Qaeda affiliate Al-Nusra Front or even the Islamic State group.
Some rebels, feeling betrayed by their international backers, may now throw their lot in with jihadist groups, Hokayem warned.
Syria's regime, meanwhile, bolstered by Russia and Shiite fighters from Lebanon's Hezbollah movement and elsewhere, is likely to consolidate its hold over "useful Syria" -- the densely populated west and coast of the country.
"What the Russians and Assad are doing is they want to control western Syria and leave the Americans to deal with the jihadist monster in eastern Syria," where IS group is most powerful, Hokayem said. "And it's working."
The rebel losses came as peace talks in Geneva collapsed, but analysts said they had always been doomed to fail.
They said Russia's intervention and the latest advances had emboldened the regime to resist any concessions, and made it impossible for the opposition to negotiate.
"Those who wanted to negotiate at Geneva would be accused of treachery, even more so given the results," said Balanche.
The UN's Syria envoy Staffan de Mistura insisted this week that the talks had not failed, and were only on hold until a new session scheduled for February 25.
Hokayem said the process was little more than "a show", but would limp on without achieving results.
"The US is happy having a process and is happy hiding behind that."