Four people have died after a pile up involving a four lorries and four cars.
At least a dozen others were injured in the fatal collision on the A34 in Berkshire.
Police have said a man has been arrested on suspicion of causing death by dangerous driving and is currently in custody.
Thames Valley Police were called to the scene near East Ilsley at 5.10pm.
One man was flown by air ambulance to the John Radcliffe Hospital with life-threatening injuries.
Two people were taken to the Royal Berkshire Hospital by land ambulance with minor injuries.
Nine people sustained minor injuries and were treated at the scene.
The northbound carriageway of the A34, between Chieveley at junction 13 of the M4 and between the West Ilsley junction, is currently closed and will remain closed for a significant time, police said.
The southbound carriageway in this area is also closed. It is likely to reopen within an hour.
Senior investigating officer Insp Andy Storey said: “Officers are currently on the scene responding to this fatal collision. All motorists should avoid the area, use alternative routes and await further updates before attempting to travel on this route."
Police are appealing for witnesses.