Detectives from the Major Collision Investigation Unit are investigating a three-vehicle collision in Pakenham South this morning.
Emergency services were called to the scene following reports of a collision between three cars on Ballarto Road, near McDonalds Drain Road, about 6.30am.
Police said it is believed a car crossed onto the wrong side of the road causing a head-on collision, with a third vehicle clipping the rear of one of those vehicles.
Four occupants from one of cars have been taken to hospital with varying injuries, including one woman who as airlifted to hospital with life-threatening injuries.
The male driver of the vehicle believed to have crossed onto the wrong side of the road was airlifted to hospital with serious injuries.
The driver of the third car was not injured.
Ambulance Victoria was called to a report of an incident in Pakenham South just after 6:30am this morning.
An Ambulance Victoria spokesperson said paramedics treated five people at the scene.
A man in his 40s was flown by air ambulance helicopter to the Royal Melbourne Hospital with serious injuries.
Two people were taken by road also to the Royal Melbourne Hospital.
One person was taken by road to the Alfred Hospital.
One person was taken to Dandenong Hospital by road.
Police said the exact circumstances surrounding the collision are yet to be determined and the investigation is ongoing.
Anyone with information or dashcam footage is urged to contact Crime Stoppers on 1800 333 000 or make a report at crimestoppersvic.com.au.