Two people were critically injured and three others hurt when a vehicle crashed on State Highway 1 near Waipahi at lunchtime on Saturday, shutting the main road between Gore and Balclutha for the second day in a row.

Police said the alarm was raised at about 12.05pm after a single vehicle crashed near Webb Road, on the part of SH1 signposted as the Waipahi Highway, in the Clutha district. In an update shortly after 1pm they put the toll at two people critically hurt and three with minor injuries, and told drivers to keep away from the area and expect hold-ups.

Hato Hone St John described the casualties a little differently. The ambulance service told 1News its crews treated two patients who were flown to Dunedin Hospital in a serious condition, while a third went by road to Southland Hospital at Kew, in Invercargill, with moderate injuries. The response, St John said, involved a pair of helicopters, one ambulance, two first response units, a rapid response unit and a manager were sent.

The Otago Southland Rescue Helicopter Trust's public mission log shows two flights to an accident at Waipahi, logged at 12.26pm and 12.38pm.

Neither police nor St John has said what sort of vehicle was involved, how the five people knew each other or where they are from. No names or ages have been released, and police have made no comment about what led to the crash.

The NZ Transport Agency said the closed section ran from the Webb Road turn-off to the one at Watt Road. The road reopened shortly after 6pm, roughly six hours after the crash, and the agency asked motorists to take care on the stretch near Waipahi.

It was the second serious crash in the same corner of South Otago in a little over 24 hours. On Friday morning a car and a tractor collided on the Waipahi Highway about seven kilometres northwest of Clinton, and police later confirmed one person had died at the scene. SH1 was closed between Clinton and Wairuna for about seven hours that day. The Otago Daily Times reported that Saturday's crash happened close to the site of Friday's.

Police have not yet named the person who died on Friday.

The two Clutha crashes follow the death of Balfour woman Kararaina (Kara) Aroha Toimata, 30, on SH6 at Josephville on Tuesday, and a fatal two-vehicle collision in the Kawarau Gorge on 30 October. The ODT reported the Transport Agency was urging people to drive with extra care because of the recent run of serious crashes across Otago and Southland.

On Friday evening, before the latest crash, Southern district road policing manager Inspector Craig Brown issued a plea for care after three road deaths in the district in a week. He said speed, unworn seatbelts, distraction and impairment were the factors police saw most often in deaths and serious injuries.

The Waipahi Highway is the route most Southlanders take to Balclutha and Dunedin, and it carries freight and farm machinery as well as cars.

Anyone with information about Saturday's crash, including dashcam footage from SH1 near Waipahi around midday, can contact police on 105. Highway conditions are posted at journeys.nzta.govt.nz and on 0800 44 44 49.