At least 30 people have been killed, state media said.
A suicide bomber has detonated an explosive vest inside the main judicial building in the Syrian capital, killing at least 25 people and wounding many others, state media said.
The bombing inside the Justice Palace, located near the famous and crowded Hamidiyeh market in Damascus, was the latest in a spate of explosions and suicide attacks targeting government-controlled areas in Syria and its capital.
It came as Syrians mark the sixth anniversary of the country's bitter civil war, which has killed more than 400,000 people and displaced millions of others.
The conflict began in March 2011 as a popular uprising against President Bashar Assad's rule but quickly descended into a full-blown civil war. The chaos allowed al Qaida and later the Islamic State group to gain a foothold in the war-torn nation.
According to Damascus police chief Mohammad Kheir Ismail, the attacker struck in the early afternoon - at 1.20pm local time. A man wearing a military uniform and carrying a shotgun and grenades arrived at the entrance to the palace, the police chief told state TV.
The guards stopped the man, took away his arms and asked to search him. At that point, the man hurled himself inside the building and detonated his explosives, the chief said.
Syria's attorney general, Ahmad al-Sayed, confirmed that account to state TV, saying that when the security guards tried to arrest the man, he threw himself inside the palace and blew himself up.
"This is a dirty action as people who enter the palace are innocent," he said, noting that the timing of the explosion was planned to kill the largest number of lawyers, judges and other people who were there at the time.
Ambulances rushed to the scene to transfer casualties to hospital.
The blast followed twin attacks on Saturday that killed at least 40 people in Damascus, an attack claimed by the Syria's al Qaida branch, formerly known as the Nusra Front.
There was no immediate claim for Wednesday's bombing, which came during a new round of peace talks in the Kazakh capital of Astana. Syria's armed opposition boycotted those talks due to what they say are ongoing government military offensives across the country.
Syria's UN ambassador said on Wednesday he was concluding his participation in the latest round of talks in Astana after two days of meetings without rebels.
Bashar Jaafari said discussions were "constructive" but only one official paper was produced -about de-mining Palmyra, the historic Syrian town that pro-government forces recaptured from the Islamic State group two weeks ago.
Syrian rebels did not send any delegates to this, third round in Astana, accusing the government and Russia - one of Damascus' main backers - of breaking ceasefire pledges and obligations to distribute humanitarian aid.
The Astana talks, brokered by Russia and Turkey, are centred on reaching a ceasefire in Syria and getting humanitarian relief to millions of suffering civilians. They run parallel to the UN-mediated political talks in Geneva aimed at ending Syria's civil war.
Meanwhile, taking stock of six years of Syria's civil war, the UN health agency said in Geneva on Wednesday that over half of all hospitals and public health centres in the country have closed or are partially functioning, and nearly two-thirds of health-care workers have fled.
The head of the World Health Organisation's emergencies program, Peter Salama, said resources to help the health care system are "stretched to the limit," citing security threats to health care workers and a lack of access to medicines and medical equipment.
Mr Salama called for "systematic and unhindered access" for life-saving materials like vaccines and medical supplies "on this sad anniversary of the start of war in Syria and before more lives are lost".