Police surround Melbourne CBD

The normally bustling Friday night hum in central Melbourne was eerily quiet as much of the CBD was locked down and hundreds of police barricaded the streets where a man ploughed his car into crowds, killing four people and injuring about 20 others.

The length of Bourke Street from Exhibition Street to William Street has been taped off while police collect evidence from the rampage that left a 10-year-old child and a man and a woman in their 30s among the dead.

Children as young as three months were left critical.

On the intersection of Bourke and William Streets, where Dimitrious "Jimmy" Gargasoulas, 26, was eventually arrested, evidence still lies on the street.

The metal frame of a pram lies near a traffic light, surrounded by pieces of clothing and a first aid kit. A bunch of flowers has been placed nearby, as people begin to pay their respects.

Many of the businesses along Bourke Street shut up shop early.

Just a couple of metres away from William Street, Bank of Melbourne worker Duran Radojcic contemplated leaving the city and going home after the attack.

"I definitely didn't want to keep working but you've got to finish off your job," he told AAP.

"It's quite surreal."

Much of the city's outer roads are clogged with traffic, while small connecting roads are overflowing with pedestrians.

Numerous trams sit abandoned on Bourke and Elizabeth Streets, due to the closure, forcing many trams to taking alternative routes.

People who live in flats in the taped off area were still unable to return to their homes early on Friday night.

Police are expected to be at the scene overnight, with road closures expected to continue until they leave.