Police are investigating a serious rollover near Glen Innes which saw one patient ejected from the vehicle and another trapped on Friday night.

The crash injured a 44-year-old woman and a man, believed to be in his late-fifties or early-sixties, when the car left the road and rolled between Glen Innes and Grafton about 6pm.

Paramedics and police as well as Fire and Rescue NSW crews from Glen Innes, the RFS and VRA volunteers rushed to the crash scene on the Gwydir Highway in the Glenelgin area.

Rescue crews used hydraulic rescue tools to free the driver from the car.

A 44-year-old woman suffered extensive injuries, a spokesperson for the Westpac Rescue Helicopter said.

The Lismore-based helicopter airlifted the woman to Lismore Base Hospital in a stable condition. 

The man suffered chest injuries and was transported by road ambulance to Glen Innes Airport where the Tamworth-based Westpac Chopper was waiting. 

He was then stablised and flown to Tamworth hospital. On Saturday, he was then airlifted again to John Hunter Hospital in Newcastle for specialist treatment.

Police are investigating the cause of the crash, which shut the highway for a short time.

Meanwhile, two cyclists were listed in a serious condition in hospital after they were struck while riding near Tenterfield on Saturday.

Police will allege a Ford Courier utility struck the men on the Bruxner Highway, about 6km east of Drake, at 11.30am.

Police said the vehicle was travelling west on the highway when it collided with the west-bound cyclists, who were riding as part of a group.

The men, aged 28 and 49, suffered serious injuries and were taken to the Gold Coast University Hospital, where they were expected to undergo surgery.

A 34-year-old man, who police will allege was the driver of the Ford and failed a roadside breath test, was arrested at the scene.

He was taken to Tabulam Police Station where he allegedly returned a blood alcohol reading of 0.243 – almost five times the legal limit.

The man was charged with eight offences including two counts each of aggravated dangerous driving occasioning grievous bodily harm (GBH) and dangerous driving occasioning GBH, as well as drive with high-range PCA and alter concentration of alcohol before a test.

He is also facing a charge of possessing a prohibited drug after police allegedly found what they allege is cannabis during a search of the Ford.

The man was refused bail to front court in Lismore.