A critically injured driver is in hospital under police guard after a two-vehicle crash in Melbourne on Sunday.

The 38-year-old Kensington man crashed at the intersection on Murray Rd and Albert St in Preston about 2.45am.

He was taken to hospital fighting for life, Victoria Police said.

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His passenger, a 28-year-old Coburg man, suffered non-life threatening injuries.

He was also taken to hospital under police guard.

The driver of the other car involved, a 41-year Preston woman, was hospitalised with non-life-threatening injuries.

One of the cars involved burst into flames after the smash, and firefighters were among the emergency services that responded to reports of the early morning crash.

The exact circumstances surrounding the incident are unclear at this stage.

Investigations are ongoing.

Two men were hospitalised under police guard, one in a critical condition, after the crash at Preston. Credit: 7NEWS

A sedan burst into flames after the intersection smash. Credit: 7NEWS