Three medical helicopters were called in following a near head-on crash late Saturday night on Route 38 in Washington Township that left both drivers trapped, authorities said.
All three occupants in both cars were flown to a Pittsburgh hospital with injuries. Their conditions were not known.
State police are investigating but an accident report was not immediately available.
The wreck happened about 11:15 p.m. on the 2100 block of Route 38, and closed the road between Bruin and North Washington roads for more than three hours.
A cause of the crash was unknown but emergency crews said road and weather conditions were not believed to be factors.
North Washington and West Sunbury volunteer firefighters responded and found both four-door sedans heavily damaged. It took rescuers about 45 minutes to get one of the drivers, a man, out of his car.
Front and back doors and the roof of that car had to be removed, authorities said, and the steering wheel and dashboard had to be lifted to free him.
The man was conscious during the entire rescue. Emergency crews said he had injuries to both legs, his back and hip.
A woman riding in that car apparently was able to get out on her own after the collision.
Rescuers removed the driver's side door to get the other driver, a man, out of his vehicle. He had a bleeding leg injury. He, too, was conscious and alert.
Firefighters set up landing zones for the helicopters on a field across from the nearby Rolling Ridge Farms.