A head-on crash in Melbourne’s North has left a road closed for more than five hours.

A white Holden Astra and white Toyota Hilux ute collided on High Street in Reservoir just before 2:20 AM on Friday.

Police were told that the two vehicles had crash head-on and now an investigation is underway.

The driver of the Toyota, a man in his 50s, has serious injuries and is in hospital.

The two male occupants of the Holden, who are in their 20s, are also in hospital under police guard.

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High Street remains closed in both directions between Hughes Parade and Asquith Street with police tape roping off the area.