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Senior Sergeant Steve Aitken, of Dunedin, said a Honda Jazz car and a heavy truck and trailer loaded with plastic pipes crashed near the intersection of State Highway 1 and Henley Rd, at the northern entrance to the Taieri River bridge, at 2.17pm.
The 66-year-old car driver was in a critical condition in the intensive care unit and an 82-year-old car passenger with serious injuries was being treated in the emergency department at Dunedin Hospital, Snr Sgt Aitken said.
The state highway was a 100kmh area, he said.
Mosgiel Police Senior Sergeant Darryl Lennane said both the car and the RX Plastics Ltd truck were travelling north.
It appeared the car had pulled over to the side of the road to let traffic pass before turning right into Henley Rd. However, when the car turned right, there was a collision with the truck, which had been following.
Snr Sgt Lennane said the truck driver was distressed after the accident but was otherwise uninjured.
State Highway 1 was closed from Berwick-Henley Rd in the south, to Centre Rd in the north, and detours were put in place.
Snr Sgt Lennane said it had been the scene of several fatal accidents in the past two years.
A 66-year-old woman was killed in a head-on collision on State Highway 1, at the northern entrance to the Taieri River bridge in February 2012; and in January this year an 80-year-old man died following a two-vehicle crash on State Highway 1, just south of the Taieri River bridge.
Snr Sgt Aitken said the state highway was reopened at 5.15pm yesterday and crash investigations were continuing.