© Nine NewsThe Nepean Highway remains closed in both directions.
A person has died in a horror head-on crash after a car allegedly crossed onto the wrong side of the Nepean Highway during the busy morning peak.
Investigators have been told a southbound vehicle crossed over into oncoming traffic on the northbound lanes and collided with another vehicle near Ti-Tree Grove at Seaford just after 6.30 am.
The driver of the northbound vehicle, who was the car's sole occupant, died at the scene. Three other people were injured.
The driver of the southbound vehicle was arrested by an off-duty police officer before being taken to hospital with non-life threatening injuries.
The Nepean Highway is expected to remain closed for hours in both directions between Eel Race Road and Station Street.
Police have not yet confirmed how many vehicles were involved in the crash.
Ambulance Victoria said paramedics treated three people at the scene.
Two people, including a woman in her 20s, have been taken to Frankston Hospital in a stable condition.
Another person has been taken to The Alfred hospital.
Major Collision Investigation Unit detectives are currently at the scene investigating the incident.
VicRoads is advising drivers to use the Frankston or Mornington Peninsula Freeways.
Anyone with information is urged to contact Crime Stoppers on 1800 333 000 or submit a confidential report at www.crimestoppersvic.com.au