The A38 from Exeter towards Bodmin is closed between the junctions with the A374, west of Plymouth, and the A390 Liskeard East, following an accident.
Two vans collided on the west-bound carriageway around 5:30am Sunday morning. Police report that four people were involved and that two have been taken to Plymouth's Derriford Hospital with serious injuries.
Inspector Andy Oliver of Devon & Cornwall Police said they are "...investigating whether one of the vehicles was in fact on the wrong side of the road when they were involved in a head-on collision with the other."
As at 10:00am Sunday morning the road is still closed, with local diversions. The road is expected to re-open from 11:00am.