Two are dead, three have been critically injured and a fourth seriously hurt after a crash near Waihola, 30 minutes south of Dunedin.
A St John spokesperson said they were alerted to the crash at 12:17pm on Monday.
The two vehicles crashed on State Highway 1, between Titri Rd and Bungards Rd.
The St John emergency response team included two helicopters, three ambulances and two rapid response vehicles.
"Two of the critically injured had been driven in an ambulance to Dunedin Hospital, and two others were flown by helicopters," the spokesperson said.
In a later statement, police said two people also died at the scene.
Inquiries into the circumstances of the crash are underway.
The highway was closed for several hours but reopened shortly after 5pm.
