Forty people were killed on Friday in a car bombing near a mosque in Damascus province, the Britain-based Syrian Observatory for Human Rights said.
The dead include women and children and many of the dozens of injured are in serious condition, activists told the observatory.
The scene of the explosion, a village called Suq Wadi Barada, is controlled by rebels, but Syrian government forces are deployed just outside the community, the activists said.
The National Coalition, representing a wide range of opposition groups, blamed forces loyal to President Bashar Assad for the blast, which occurred just as worshippers at the mosque were concluding Friday prayers.
Official news agency Sana attributed the attack to "terrorists".
The United Nations estimates that Syria's internal conflict has claimed more than 100,000 lives since March 2011, when violence erupted in the wake of harsh government repression of peaceful protests.
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