At least 53 people, most of them civilians, have been killed and 237 others injured in a powerful car bomb near the ruling Baath Party headquarters in central Damascus, state media says.
Syrian Television described Thursday's blast in the capital's central Mazraa neighbourhood as a "terrorist attack".
Opposition activists also reported the explosion, with the UK-based Syrian Observatory for Human Rights (SOHR) saying that at least 42 people had been killed. It said nine of the dead were members of government forces while the rest were civilians.
SOHR said that dozens of the wounded were in critical condition.
The main opposition group, the Syrian National Coalition, also denounced those responsible as "terrorists", saying that the opposition was not responsible for the bombing.
The pro-government TV station Al Ikhbariya showed images of what appeared to be at least four dead bodies on the ground and cars on fire.
The footage shows firefighters trying to douse cars on fire and lifeless bodies lying on the grass of a public garden.
Witnesses at the scene said a car had exploded at a security checkpoint between the Russian embassy and the central headquarters of the ruling Baath Party of President Bashar al-Assad.
Ambulances went to the scene of the blast, which also shattered windows and sent up a huge cloud of smoke visible throughout much of the city, witnesses said.
"It was huge, everything in the shop turned upside down," one local resident said, speaking on condition of anonymity for fear of retribution for speaking with foreign media.
In a statement posted on Facebook, the Syrian National Coalition stressed that "any acts targeting civilians with murder or human rights violations are criminal acts that must be condemned, regardless of the perpetrator or the justification".
Al Jazeera’s Rula Amin, reporting from Beirut in neighbouring Lebanon, said the explosion took place in a heavily fortified area.
"The city is under very strict restrictions. People who have come out of Damascus have been telling us about how many checkpoints are there within the city limits, inside the neighbourhoods and between different areas; especially around the headquarters of the Baath Party, the security installations and the presidential palace," she said.
"So it seems that whoever was behind the attack had managed to go through many checkpoints until they got to the point where they can explode the car."
The explosion comes amid reports of fierce clashes over the past few days between the opposition and government forces around Damascus, as rebels tried to make advances in the city.
The car bombing was followed soon after by a mortar attack on a military headquarters, both government-sponsored media and opposition activists reported, without giving information on casualties.
A security official reported another blast in Damascus' northeastern Barzeh neighbourhood.
He had no other information and spoke on condition of anonymity because he was not authorised to brief the media.
Thursday's blasts followed two mortar attacks in as many days on Damascus and came as anti-government activists reported that air attacks in the southern city of Deraa had killed at least 18 people.
On Wednesday, two mortar shells exploded near a football stadium in Damascus, killing one player.
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The day before, two mortar shells went off near one of Assad's three palaces in the city, causing only material damage.
Damascus has so far mostly avoided the large-scale violence that has destroyed other Syrian cities, though deadly car bombings have targeted government buildings in the capital.
The latest development came as a major opposition meeting was under way in Cairo, the Egyptian capital.
In a communique drafted for Thursday's meeting, the Syrian National Coalition said it was willing to negotiate a peace deal to end the conflict in Syria but that Assad cannot be a party to any settlement.
The document, seen by Reuters news agency, said Assad and his cohorts must be held accountable for bloodshed and that any peace deal must be under the auspices of the US and Russia.