The scene of the crash on the M5 Six articulated lorries were involved in the collision, the fire service said
"Several" people were killed and up to 35 injured in a 27-vehicle crash on the M5 near Taunton, Somerset, police say.
Officers said the crash, which happened close to junction 25 northbound at about 20:30 GMT on Friday, led to "one massive fireball" at the scene.
Emergency crews said the cause of the crash was not clear, but there had been reports of heavy rain and fog.
Avon and Somerset Police have released a helpline number for people concerned about relatives: 0800 092 0410.
The stretch of motorway is due to remain shut in both directions until at least 12:00 GMT on Saturday.
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The M5 is currently shut northbound between junctions 25 and 24, and southbound between junctions 23 and 25. Some drivers reported delays of up to five-and-a-half hours and motorists have been urged to avoid the area.
Assistant Chief Constable Anthony Bangham, of Avon and Somerset Police, said "several people" had died but he could not be specific about numbers at this stage.
He said: "The incident was very, very challenging and on arrival crews were faced with literally one massive fireball.
"Most vehicles were well alight and most continued to burn for a considerable time. This made it very difficult to search the vehicles. Some of them have been burned to the ground."
Emergency crews said they believed the weather may have been a contributory factor in the crash, with witnesses describing having seen thick fog at the time.
Earlier, part of nearby Bridgwater town centre had been closed off amid fears a wall could collapse after heavy rain.
Paul Slaven, of Devon and Somerset Fire Service, said crews were "damping down" at the scene of the crash, which he said was "the worst road traffic collision anyone can remember".
He said: "There is a large amount of debris covering the road and a couple of vehicles are still smouldering after being on fire so the police have said the road will be closed for at least 24 hours and possibly more for the carriageway to be cleared."
The fire service said there had been 20 "light vehicles" involved in the incident, along with six articulated lorries.
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Motorist Steven Swift, who passed the accident scene while heading south about 30 minutes after the crash, said he had seen three lorries on fire and some injured people lying in the central reservation.
He added: "It was a horrific scene. The heat was intense."
Bev Davis, who had been in a field near the motorway looking after her horses, said: "There was this horrific sound of a horn. The horn was just permanent.
"You knew something had gone on and then the flames were just so high so quickly and the noise was horrific. And then there were explosions, I think probably of tyres going."
She added: "From where we were standing we could only see what was directly in front of us because the flames and smoke were smothering everything. There must have been 200m-worth of fire - plumes of smoke were going up and everything was red."
Coach driver Michael Wagner said he had "never seen anything like this".
He said: "There were lots of lorries on fire. There was a car underneath one of the lorries.
"It looked like two lorries had jack-knifed at the front. In all, there must have been eight or nine lorries and 15 cars behind them. There was smoke and flames everywhere."
Traffic queues on the M5 in Somerset Long tailbacks were reported on the motorway following the crash
He said there was debris "everywhere, even on the southbound side".
Jaysen Sharpe, who had been at nearby Taunton Rugby Club which had been hosting a fireworks display at about the time of the crash, said he had seen "a number of explosions, petrol tanks that I believed were going up".
Motorist Steve Burge said he had seen two lorries on fire and a car which had been almost burnt out.
"It was something that you wouldn't want to see," he said. "It was an image that will stick with me forever."
Driver James Starkey, who was caught up in the tailbacks about 500 yards from the crash, said a "huge, billowing tower of smoke" had been rising from the scene since about 21:00 GMT.
"Police have said that we will be turned around as soon as possible, but with the amount of vehicles to turn and get moving it could be a long time," he said.
"The atmosphere among people waiting on the motorway is one of shock."
The Highways Agency said the motorway closure had affected people leaving the Bridgwater Guy Fawkes Carnival.
Andrea Day, from Trafficlink, said one of the busiest routes on Saturday would be the A38 through Taunton and warned of disruption throughout the weekend.
Taunton Dean MP Jeremy Browne said it had been a "horrendous accident".
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