Hassan Abboud, the leader of the Syrian Islamist insurgents Ahrar al-Sham has been killed with other top commanders in a bomb blast at a meeting.
Activists say a suicide bomber detonated a vest in the attack in the north-western town of Ram Hamdan.
Ahrar al-Sham is part of the Islamic Front, a coalition of seven Islamist rebel groups.
In February, Ahrar al-Sham blamed the rival Islamic State group for an attack which killed several of its members.
Activist groups say at least 40 people may have died in the attack, although the exact death toll is not clear.
Ahrar al-Sham is one of the biggest rebel groups fighting the government of President Bashar al-Assad.
Although the group is hard-line Islamist in orientation, it has opposed and clashed with the ultra-radical Islamic State (IS) group, which is the most likely quarter to be blamed for the attack, reports the BBC's Jim Muir.
IS was blamed when another Ahrar al-Sham leader, Abu Khaled al-Suri, was killed in a suicide bomb attack on his headquarters in Aleppo in February.
The death of Hassan Abboud comes at a moment when the Americans are seeking to unify the Syrian opposition into a coordinated fighting force against IS, although Ahrar al-Sham would have made an unlikely partner in such an American-led campaign, our correspondent says.
In an interview with the BBC in June, Abboud had denounced IS, saying it represented "the worst image ever of Islam".
Abboud said that, unlike IS, Ahrar al-Sham would never pledge loyalty to outsiders and would only fight in Syria. It would continue fighting until Assad's government was ousted, he said.
He also stressed that the Islamic Front did not use suicide bombers and did not follow the "takfiri" doctrine, which holds that society has reverted to a state of unbelief, legitimising attacks on other Muslims.
At one time Ahrar al-Sham was considered the most powerful rebel force battling the government, operating all over the country and sometimes co-operating with more moderate forces.