A man and a 12-year-old girl have died after a truck hit a four-wheel drive north east of Melbourne.

Police believe the truck may have crossed onto the wrong side of the road when it hit the four-wheel drive at Steels Creek just before 9am (AEDT).

The male driver of the four-wheel drive, aged in his mid 30s, and his female rear passenger, aged 12, died at the scene.

A boy, eight, and a girl, 12, were also passengers in the four-wheel drive but were uninjured and taken to hospital for observation.

The truck driver, 45, was also uninjured and he is assisting police with their inquiries.

Major Collision Investigation Unit detectives are investigating and want to hear from anyone who saw the crash or any of the vehicles leading up to it.

Detective Sergeant Chris Carnie said it was a distressing scene for emergency workers.

“Any time you have a collision such as this where children are involved, it is especially difficult,” he said.

The state road toll now stands at 38 compared to 30 this time last year.

In a separate crash earlier on Saturday, a motorcyclist died after losing control on a bend at Hoddles Creek, east of Melbourne.

The Watsonia man aged in his 40s was riding with a group of other riders, when the crash occurred about 11am.