One person is dead and the Western Highway is closed between Horsham and Dimboola after a truck and bus collided in the early hours of this morning.

Emergency services treated multiple victims at the scene three kilometres West of Pimpinio.

Acting sergeant Robert Martin said the Melbourne-bound B-double truck was travelling towards Horsham and the driver overcorrected when the truck ran off the road.

"The prime mover became disconnected and the trailers rolled onto the side."

"A passenger bus travelling the same direction ran into the trailers."

"Paramedics treated 50 people at the scene and all have been taken to Wimmera Base Hospital.

"Some have significant injuries but none are life-threatening.

"Unfortunately one person has died in the accident."

Police media have reported the bus driver died in the crash.

The highway was closed in both directions as a result of the crash with diversions in place.

Detectives from the Major Collision Investigation Unit are attending the scene.