Major Collision Investigation Unit detectives are en route to a serious crash in Seymour, Victoria Police say.
It is believed a single vehicle was travelling along Lambing-Gully Road about 9.40pm when it lost control and veered off the road, striking a tree.
The male driver, aged in his 20s, sustained minor injuries.
A male passenger, aged in his 20s, sustained non-life threatening injuries and is being assessed by paramedics, while a female passenger in her 20s has been airlifted to hospital with life-threatening injuries.
The road is closed in both directions towards Highlands Road.
Anyone with information is urged to contact Crime Stoppers.