A suicide bomber blew himself up in central Damascus on Sunday, killing at least 12 people according to the Syrian Observatory for Human Rights.
More than a dozen more were injured in the explosion -- and the SOHR said it expects the death toll to climb.
Syria's Health Minister Nizar Yazigi said injuries sustained by the victims ranged from minor to severe, state media reported.
Authorities had been pursuing three cars and were able to intercept two and destroy them, state media said.
As they closed in on the third car near the city's Al-Tahrir Square, the suicide bomber on board detonated it.
Damascus is rarely hit by attacks. Since the start of the Syrian conflict, government troops and allied militias have held a tight grip on the capital.
In March, rebel groups launched a surprise attack in northeastern Damascus, taking advantage of Syrian regime forces overstretched by fighting elsewhere in the country, an expert said at the time.
The Syrian regime has been weakened in the capital -- located in the south of the country -- due to its focus on fighting Isis in Raqqa, in the north, said Andrew Tabler, a senior fellow in Arab politics at the Washington Institute for Near East Policy.