"The 48 Iranians have been released and are being taken to Damascus, accompanied by Iranian and Syrian officials," Bulent Yildirim, head of humanitarian aid agency IHH, told Reuters by telephone from Damascus.
He said the release of 2,130 civilian prisoners, most of them Syrian but also including Turks and other foreign citizens, had begun in return. Two state-run Iranian television channels also reported that 48 Iranians had been freed in a swap.
There was no confirmation from the Syrian government, which has periodically freed hundreds of prisoners over the 21-month-old conflict in apparent concessions. But Damascus has always stressed such prisoners "do not have blood on their hands."
Syrian government forces have struck local deals with rebel groups to trade prisoners but the release announced on Wednesday would be the first time non-Syrians were freed in a swap.
Opposition groups accuse Assad of detaining tens of thousands of political prisoners during his 12 years in office and say those numbers have spiked sharply during the civil war.
Missing persons became a key issue when street protests against Assad first erupted in March 2011.