Two people were killed and a third person remains in a critical condition in the Alfred Hospital after a B-Double truck travelling west on the Western Highway veered onto the wrong side of the road and collided with a semi trailer travelling east head-on.

A third semi-trailer was unable to stop in time and collided with the rear of the semi travelling east.

A fire started before all of the vehicles erupted in flames. The fire spread to near-by grassland and burned for several hours until fire crews were able to bring it under control just after 6am this morning.

One of the trucks was carrying household products, including aerosol cans, while another other was transporting cars.

Major ColIision Investigation Unit Detective Sergeant Darren Williams said it is going to be a hard task formally identifying the deceased with members from the Disaster Victim Identification team now on site.

"The road is badly burnt, charred, there is so much debris. It's just one of those things, this is the real horror of road trauma," he said.

"Walking through that scene you just... people just don't have any realisation of what it's like. 

"I mean this is like bushfire stuff, that is just how hot this fire was.

"And just before Christmas, yes we have 20 days to go and two people who aren't going to make it."

Police are receiving a large number of calls from members of the public seeking information on those involved in the collision.

People concerned about the location of their family members who are truck drivers and were possibly in the area last night and who have not heard from them or have been unable to contact them, are asked to contact trucking companies or employers in the first instance.

Any trucking companies with queries should contact Ararat Police Station on 5355 1500.

Police ask that only trucking companies contact police and members of the public use the process outlined about in the first instance.

The Western Highway between Stawell and Great Western is expected to remain closed until after dark.