Police at the intersection of Elizabeth and Lonsdale streets after the motorcycle crash. Credit:Bart Lewis

A motorcyclist may have been fleeing from police when he crashed in Melbourne's CBD, suffering a serious head injury.

The rider, a man in his 30s, came off his Harley-Davidson near the intersection of Elizabeth and Lonsdale streets about 9.15am on Wednesday.

Police spokeswoman Alex Day said while it appeared the rider had accelerated away from police at the time of the crash, a police pursuit had not taken place.

"State Highway Patrol members were conducting an intercept with un-related vehicle on Elizabeth Street shortly after 9am when they observed a motorbike rider wearing what is believed to be a non-compliant helmet," she said.