At least 48 Iranian pilgrims who were returning from a Shiite shrine of Sayyida Zainab were abducted from their bus near the Syrian capital Damascus.
The pilgrimage site in the Shia majority district of Sayyida Zainab is visited by thousands of Iranians every year.
The pilgrims were reported to be on their way back to the airport when the incident happened on 4 August, Iran's state news agency IRNA reported.
However, there were conflicting reports about the incident. Iran's state-owned television al-Alam, citing an official at the Iranian embassy in Syria, reported that the pilgrims were heading towards the shrine when they were kidnapped.
Iran blamed armed groups for the incident and claimed they knew the whereabouts of the abductors.
According to Syrian news agency Sana, the Iranians were abducted by "armed terrorist groups" and Syrian authorities were working to handle the situation.
It is the latest in a series of recent abductions involving Iranian pilgrims but the Sayyida Zainab incident is the single largest kidnapping reported so far. In most cases the pilgrims were freed afterwards, according to government claims.
In May, 11 Lebanese Shia pilgrims who were on their way back from Iran were abducted in Syria. Though they had been declared released from the captors, their whereabouts remain in mystery which even led to sectarian violence across Lebanon.
Iran is a close ally of Syria which is under the Alawite-dominated regime, an offshoot of Shiite Islam. The Sunni-dominated opposition is engaged in fierce fighting with government forces in Syria to oust the regime.
Meanwhile, fresh violence was reported in Aleppo and the southern neighbourhood of Tadamon, on the outskirts of Damascus.
"We heard heavy bombing since dawn. Helicopters are in the sky," a witness in Damascus told AFP.