A key group within the Syrian opposition National Coalition said Sunday it would not attend proposed peace talks in Geneva and would quit the Coalition if it participated.
The decision deals a potential blow to international efforts to convene a peace conference in Geneva, which was first proposed for June but has been pushed back multiple times.
The Syrian Red Crescent meanwhile said it had evacuated around 1,500 people from a suburb of the capital Damascus that has been under a regime siege for months.
The president of Syrian National Council, the biggest member of the opposition Coalition, told AFP on Sunday that it was impossible to carry out negotiations given the suffering of people on the ground.
"The Syrian National Council, which is the biggest bloc in the Coalition, has taken the firm decision... not to go to Geneva, under the present circumstances (on the ground)," George Sabra told AFP.
"This means that we will not stay in the Coalition if it goes" to the peace talks, he added.
Western nations and Russia have been pushing the regime and the rebels to meet for talks on a negotiated solution to the two and a half year-old conflict, which has killed some 115,000 people.
US Secretary of State John Kerry flew to London on Sunday for talks that will include discussion of the Geneva conference with Lakhdar Brahimi, the UN-Arab League envoy for Syria.
But Sabra said the international community had failed to punish the regime for an August 21 sarin attack on the outskirts of Damascus that reportedly killed hundreds of people.
Washington threatened to carry out military strikes in response to the attacks, which the United States and the Syrian opposition blamed on the regime.
But the punitive strikes were averted by a US-Russian deal under which Syria is turning over its chemical arsenal for destruction.
"The international community has focused on the murder weapon, which is the chemical weapons, and left the murderer unpunished and forgotten the victims," Sabra said.
"The regional and international context does not give the impression that Geneva 2 will offer anything to the Syrians," he added.
"We will not participate in a conference that is intended to hide the failure of international politics."
He also invoked the plight of Syrians in neighbourhoods besieged by regime troops, including in the Damascus suburb of Moadamiyet al-Sham, where he said residents were "dying of hunger."
The suburb southwest of the capital is largely controlled by rebels and has been under an army siege for months.
On Sunday, the Syrian Red Crescent said it had evacuated 1,500 people from the neighbourhood since the day before.
"Around 1,500 people, most of them women and children, were evacuated from a point on the outskirts of Moadamiyet al-Sham and taken to shelters," Red Crescent head of operations Khaled Erksoussi told AFP.
He said the evacuated civilians "were in a state of major fatigue and were very scared."
Regime forces regularly bomb the area and the opposition accuses the government of starving residents by sealing off the district.
Moadamiyet al-Sham was also one of the areas targeted in the 21 August sarin attack.
The Syrian government says the opposition is holding residents of the district hostage and described the evacuation as part of its "efforts to protect citizens from terrorists."
A video distributed by state news agency SANA showed hundreds of people, mostly women and children, streaming towards a convoy of buses, assisted by officials from the Red Crescent.
State television showed Social Affairs Minister Kinda Shmat and soldiers welcoming the evacuees as they arrived.
Erksoussi said Red Crescent officials were unable to enter Moadamiyet al-Sham "to provide treatment to the wounded, who we were not able to evacuate."
He would not say whether the evacuation was the result of an agreement between the rebels and the regime, saying only that the Red Crescent "received guarantees that it could carry out this operation."
Elsewhere in the country, the Observatory said regime war planes bombed the town of Sfeireh in northern Aleppo province as they pressed a bid to reclaim the town from rebels.
Sfeireh is near a site believed to hold chemical weapons, and the regime bombardment in recent days has provoked an exodus.
In the southern Daraa province meanwhile, rebels brought down a regime warplane in the Atman region, the Observatory said.