TWO people are dead after a collision at Black Range, near Stawell, on Wednesday night.
Another man remains in a critical condition at Melbourne's The Alfred hospital.
Investigators believe a B-Double truck travelling west on the Western Highway and a semi trailer travelling east collided head-on about 11.30pm.
A third semi-trailer driver and the sole survivor was unable to stop his vehicle in time and smashed into the rear of the semi travelling east.
All vehicles went up in flames.
Ambulance Victoria spokesman John Mullen said the survivor, a man in his 50s, had severe, full-thickness burns to most of his body.
"He also had burns to his airways, and fractures," he said.
Ambulance Victoria paramedics treated the man at the scene, before taking him to Stawell Hospital.
He was then flown to The Alfred hospital in Melbourne.
Hospital spokeswoman Hannah Chipp said the man had been critically unwell but later his condition was downgraded to serious but stable.
She stressed the man was still seriously ill.
Police believe one of the trucks was carrying hair products in aerosol cans, while the others were carrying general goods.
Traffic is being diverted away from the Western Highway near Churchill Crossing Road, Black Range.
The Western Highway will remain closed until at least midday as the investigation continues.
District 16 Country Fire Authority operations manager Chris Eagle said fire-fighters had been there since about 11.30pm.
He said 20 vehicles attended during the night.
Units from Stawell, Great Western, Ballarat, Wendouree and Ararat were still at the scene, sifting through hot spots in the wreckage.
Mr Eagle said breathing apparatus crews were coming from Willaura, Beaufort and Horsham to help.
"We are hopeful that within the next couple of hours, we can hand over to Victoria Police for their investigations," he said.
Police will prepare a report for the coroner.
The Western Highway is closed in both directions between Stawell and Ararat.
Emergency Services are on site.
Traffic is being detoured from Ararat to Pomonal and Pomonal to Stawell.
Detours are as follows: Ararat-Halls Gap Road, to Pomonal; Stawell-Pomonal Road, to Stawell.
A VicRoads spokeswoman said the organisation aimed to have the road open as soon as possible after the site was handed over by police and emergency services.
She said at this stage, it was unknown when the road would reopen.
She said people could visit the VicRoads website at http://traffic.vicroads.vic.gov.au for the latest road closure information.