A woman and a teenage girl were seriously injured in a crash between a car and two lorries that forced the closure of the M6 for several hours.
The motorway was shut between junctions 13, for Penkridge, and 12, for Cannock, Staffordshire, after the crash at about 02:15 GMT.
The female car driver is believed to have suffered life-threatening injuries, the ambulance service said.
The girl, who was a passenger in the car, was also seriously hurt.
The pair had to be cut free from their white Toyota by fire crews, Staffordshire Police said.
The full closure of the motorway at junction 13 was lifted by 14:00 GMT, National Highways said.
Two lanes were shut between the entry and exit slip roads at junction 12 for several hours to enable the removal of the lorries, a spokesperson added.
The lorry drivers had remained at the scene to speak to officers, police said.
The force has appealed for anyone with dashcam footage of the crash to get in touch.