A man and woman from South Shields have been taken to hospital with serious injuries.
The Great North Air Ambulance Service (GNAAS) said the man, who was driving one of the three vehicles involved on the A66 near Whinfell Forest in Cumbria, suffered multiple life-threatening injuries.
After treatment from the trauma team the 67-year-old from South Shields was flown to the James Cook University Hospital in Middlesbrough where he arrived in a critical condition.
Police confirmed that the woman, 67, who was in the same car - a Nissan Qashqai - and is also from South Shields, was also taken to hospital in Middlesbrough with serious injuries.
A Dutch-registered Renault Master van and a Renault Scenic were also involved in the crash which took place at 11am today.
A 44-year-old man from Holland, who was driving the van, has been arrested on suspicion of causing a serious injury by dangerous driving.
His passenger was taken to the Cumberland Infirmary with minor injuries following the collision .
The occupants of the Scenic were uninjured.
Collision investigation work has been carried out and the road is now open.
Police are appealing for witnesses to a collision to contact PC Euan Stitt of the North Cumbria Mobile Support Group on 101.