Major Collision Investigation Unit detectives are investigating a fatal multi-vehicle collision in Armstrong on Wednesday where three people have died.

It is understood two cars, a B-double and two smaller trucks were involved in a collision on the Western Highway, near the intersection of Thomas Road about 12.30pm.

At this early stage, the exact circumstances of the collision are yet to be determined and investigations are ongoing.

UPDATE Thursday May 29: Two occupants of an Isuzu van, a 49-year-old male driver from Lyndhurst and 24-year-old female passenger from Clyde North, was died at the scene.

The male driver of a Toyota Kluger, a 65-year-old South Australian man, also died at the scene.

The driver of the semi-trailer, a 63-year-old Horsham man, and driver of a Volvo XC40, an 83-year-old Geelong woman, were taken to hospital with minor injuries.

The driver of an Isuzu small truck, a 52-year-old Corio man, was taken to hospital as a precaution.

The Western Highway has reopened between Stawell and Ararat.

Anyone who witnessed the incident, has dashcam footage or any other information that could assist police is urged to contact Crime Stoppers on 1800 333 000 or submit a confidential report online at www.crimestoppersvic.com.au.