At least 44 people died when two buses collided near the Iranian city of Qom, say local news reports.
The accident happened late on Monday when a tyre on one of the buses burst and it swerved into oncoming traffic, hitting the other bus head-on.
Dozens of passengers said to have been injured in the accident were taken to hospitals in Qom.
Iran has one of the worst road safety records in the world, though it has been improving over recent years.
In the 1990s, there were about 28,000 deaths per year for the country's four million cars, reports AFP news agency.
But over the past two years the number of fatalities has dropped to about 20,000 despite car numbers soaring to 17 million.
The agency says a greater police presence on the roads coupled with a stiff rise in fines for dangerous driving has helped curb deadly accidents.
Monday's accident is said to have taken place at about 23:00 (18:30 GMT) on the highway between the capital Tehran and the city of Qom to the south.
"The driver of a bus travelling from Isfahan lost control of his vehicle after one of his tyres burst," Col Ardeshir Jamshidi-rad, the head of traffic police in Qom province, was quoted as saying by AFP.
"He hit a car before finding himself in the oncoming lane, where he hit another bus. The two vehicles caught fire immediately," he said.