A man has died in a motorway pile-up involving 30 vehicles and more than 60 people on the M40 near Bicester.
A witness described the scene as "carnage" the turned the road into a "sea of metal" and debris from crushed cars.
Another person is fighting for their life in hospital and six more are being treated for serious injuries.
Six people were hospitalised with minor wounds, police said, and 49 drivers and passengers had been assessed at the scene.
The motorway remains closed northbound between junctions 9 and 10 as recovery work and investigations continue.
The accident came an hour after three men were killed on the M1 near Flitwick in Bedfordshire when their car was hit by a coach while it was parked on the hard shoulder.
Chief Inspector Henry Parsons, of Thames Valley Police Roads Policing, advised drivers to avoid the area around the M40 crash.
Blurry live Highways Agency shot of emergency services on the scene at J9 southbound M40... pic.twitter.com/R5CU3CwYUA— Neil Mossey (@NeilMossey) February 14, 2015
He added: “The cause of this collision is under investigation, however, we believe that fog played a major part.
“This has been an extraordinarily large collision, we have not had a collision on this scale for many years in Thames Valley and one man has sadly lost his life.
“We are working as quickly as possible to clear the area and get the traffic moving again."
Fire crews, police, ambulances and air ambulances were called to the motorway just before 7.50am to reports that dozens of vehicles had crashed.
Images from live traffic cameras showed miles of queues and fleets of emergency vehicles lining the road near the scene as a trickle of cars passed in the other direction.
Zara Smith, 31, was travelling from Croydon in south London to Stockport with her fiance for a family holiday when they saw dozens of ambulances and police cars whistle past as traffic came to a standstill.
"It was really thick fog and difficult to see that far in front so no one really knew what had happened. We were there for an hour and a half and then police diverted us down a slip road," she said.
"It was at that point that the fog started to rise and a mile ahead you saw this carnage.
Stuck northbound on M40! pic.twitter.com/7QIm2MYfdu— zara (@zarascakes) February 14, 2015
"There was one large lorry which had jackknifed and was across three lanes of the motorway, and all these cars ahead of it. It looked like a sea of metal.
"There was a lot of debris. We hadn't been aware of how close we actually came to it because of the thick fog.
"It was really dense fog. For about half an hour driving before the accident we were going in and out of patches of fog. By the time we stopped we could only see one or two cars in front.
"The crash was shocking. We had stopped for coffee and petrol on the way and you think 'God, if we hadn't have stopped we could have been in it', but you can't think that way."
Drivers earlier reported long tailbacks with traffic at a complete standstill and police are urging drivers to find a different route.
An ambulance spokesperson said: "We were called at 7.48am to reports of a multiple road traffic collision on the M40, junctions 9 to 10 northbound.
“I understand that there are about 30 vehicles involved.
“We have a lot of resources on the scene - ambulances, our helicopter ambulance, rapid response vehicles, our doctor and our hazardous area response team. Fire and police are also at the scene.”
West Ham was advising its fans to avoid both the M1 and M40 on their way to a match against West Brom. There are fears that Millwall fans trying to see their team play at Leeds could also be caught up in the gridlock.
Meanwhile, two Boeing 747 fuselages were being driven along the M4 and M5, causing delays and congestion.
Traffic jam going south on M40 just before Oxford junction pic.twitter.com/7MiWkCLf1e
— Jonathan Todd (@Jonathan_Todd) February 14, 2015
The large load is being taken from Kemble airfield in Gloucestershire to a scrapyard in Herefordshire.
Additional reporting by PAReuse content