Major Collision Investigation Unit detectives are investigating following a serious multi-vehicle collision at Pakenham South this morning.
Investigators believe a white utility collided head-on with a silver SUV on Healesville-Koo Wee Rup Road about 8am.
The female driver of the SUV sustained life-threatening injuries and was airlifted to hospital.
Her two passengers, both young children, sustained non-life-threatening injuries and were transported to hospital as a precaution.
The male sole occupant of the utility was also airlifted to hospital with life-threatening injuries.
Investigators have been told the white utility collided with several other vehicles prior to the head-on collision, causing minor damage to those vehicles.
Police are investigating the circumstances surrounding the collision and it remains ongoing.
Drivers are advised the road is closed in both directions at Soldiers Road and will remain shut for some time while investigators process the scene.
Anyone who witnessed the collision or with dashcam footage is urged to contact Crime Stoppers on 1800 333 000 or submit a confidential report at www.crimestoppersvic.com.au.