At least 29 people were killed, most or all of them believed to be rebels, in the besieged Old City of Homs when a car bomb exploded, the Syrian Observatory for Human Rights monitoring group said.
"The death toll is likely to rise because there are dozens of people missing and body parts in the area of the blast," the Britain-based group said on Sunday.
State news agency SANA also reported the blast, saying a car had exploded while being loaded with explosives.
One activist network, the Syrian Revolution General Commission, said the blast was the result of a rocket landing on an ammunition depot in the area.
The claim could not be independently confirmed.
The blast took place on the outskirts of the Old City of Homs, which is under rebel control.
Some 1,400 civilians were able to leave the area this year under UN supervision, but an estimated 1,500 people remain under the army siege.
In a separate development in northern Aleppo province, 30 people were killed in government air raids with explosive-packed barrels bombs, an Al Jazeera Arabic correspondent reported.
Damascus Opera House hit
In the capital, meanwhile, two people were killed when mortar fire struck the Damascus Opera House, state media reported.
"Two people were killed and five wounded by a mortar round that hit the Damascus Opera House" near key government and military buildings on Umayyad Square, state-run SANA news agency reported.
The attack damaged the Opera House, which was inaugurated by President Bashar al-Assad in 2004.
Mortar fire also wounded 13 people in several neighbourhoods of the capital.
On Saturday, mortar rounds struck near the Russian embassy, said the Observatory.
The rebel fire on Damascus comes as government forces step up a campaign to crush fighters in its eastern suburbs, it said.
On Sunday, the Observatory said five civilians, including three children, were killed in regime air strikes on the town of Douma northeast of Damascus.
And additional air raids as well as fierce fighting was reported in Mleiha, southwest of the capital in Damascus province.