Two people were killed today after more than 100 vehicles were involved in a pile-up on the M40 southbound in Oxfordshire, Thames Valley Police said.
At least 20,000 vehicles are now stuck in a 15-mile tailback, which will take at least two more hours to clear.
The accident happened at about 7am in thick fog when a motorcyclist and a van were in collision on the south-bound motorway at Lewknor.
A spokesman for Thames Valley police said at least one person had been killed in the crash and there were "many walking wounded".
Police described the pile-up as "a major accident" and urged drivers to avoid the area completely as the fog was still causing problems.
Officers were called to the scene at 7.05am and ambulance and fire services arrived soon afterwards.
He said the initial crash, between Oxford and High Wycombe in south Oxfordshire, "caused a series of knockon collisions".
Thames Valley Police said there may be more fatalities but it was too early to tell.
The M40 southbound was closed between junctions five and eight and officers appealed to drivers on the northbound carriageway not to slow down to look at the scene.
A spokesman for Thames Valley Police said: "The fog is still pretty thick out there and we are urging drivers to avoid the area completely."Reuse content