Twenty-one people, including four children and six women, were killed when a minibus exploded in the southern town of Noa, a monitoring group said.
The truck was passing through rebel-held territory in Syria's Deraa province but there are also government troops in the nearby base of Tel al-Jumaa, which is besieged, the UK-based Syrian Observatory for Human Rights said.
Opposition activists told the British-based Observatory, which is opposed to President Bashar al-Assad, that the minibus drove over a mine planted by government forces. There was no immediate comment from the government.
Deraa was the birthplace of the Syrian uprising against Assad in March 2011.
Al Jazeera's Omar Al Saleh, reporting from neighbouring Turkey, said the blast was close to a Syrian government air defense unit, which is why opposition activists are accusing the government of having mines in the area.
Violence has continued despite pleas from regional Arab and Muslim organisations for a ceasefire to mark the Muslim festival of Eid al Adha.
The Observatory says more than 115,000 people have been killed in the war that erupted after Assad's troops unleashed a brutal crackdown against protesters, calling for political change against his family's four-decade grip on the country.
The group said at least 27 government soldiers had been killed during intense clashes in the eastern city of Deir al-Zor over the past two days although rebels gave a figure more than double that.