UPDATE 9.25am: Police have confirmed the man killed in a crash at Kangaroo Flat overnight was a 35-year-old from Epsom.
Sergeant Mick McCrann, from Bendigo Highway Patrol, said the man was driving a Toyota Yaris in the westbound lane of Lockwood Road when the car crossed onto the wrong side of the road and collided with a Nissan Patrol.
The man was pronounced dead at the scene.
The other male driver was uninjured, but was taken to Bendigo Health for examination and blood tests.
Sergeant McCrann said there was no suggestion the driver of the Nissan Patrol was in any way at fault, and it appeared that wildlife also did not play a role in the crash.
The crash was attended by Bendigo police, SES, CFA and paramedics.
The road was closed or significantly restricted to traffic until about 8.30am as police undertook investigations at the scene.
Bendigo Highway Patrol will prepare a brief for the coroner.
EARLIER: A man has died following a two-car crash in Kangaroo Flat in the early hours of Friday morning.
Emergency services were called to the scene shortly after 2.15am following reports of a head-on collision on Lockwood Road.
Investigators are yet to establish the exact circumstances surrounding the collision, but it is believed a car travelling towards Kangaroo Flat swerved onto the other side of the road and struck an oncoming vehicle.
The male driver of the first vehicle, who is yet to be formally identified, died at the scene.
The driver of the other vehicle, a man aged in his 50s, did not suffer any injuries.
Road closures are in place and the investigation is ongoing.
Anyone who witnessed the collision is urged to contact Crime Stoppers on 1800 333 000 or submit a confidential report at www.crimestoppersvic.com.au