Police confirmed the crash was at the intersection of the Calder Alternate Highway and Calder Highway about 7pm. 

The Bendigo Advertiser incorrectly reported earlier the crash occurred in Lockwood.

Senior Constable Brian Smith of the Bendigo Highway Patrol said a Melbourne man, 32, failed to give way at a stop sign.

He said the Melbourne man's car collided with a vehicle travelling toward Bendigo. 

He said the Melbourne man was airlifted to the Royal Melbourne Hospital with back injuries. 

Senior Constable Smith said a 59-year-old Moama man in the Bendigo bound car was taken to Bendigo Hospital with cuts and abrasions. 

He said the Melbourne man would be issued with a penalty notice for failing to give way at a stop sign. 

"At this time of year people have to be really careful," he said. 

"People need to take notice of what's going on around them." 

Ambulance Victoria spokesman John Mullen said the Melbourne man was in a serious but stable condition. 

He said another two men were taken by ambulance to Bendigo Hospital with minor injuries.