At least seven people have been killed and as many as 51 injured in a collision involving 34 vehicles on the M5 in Somerset.
Seven articulated lorries and other light vehicles were involved in the smash on the motorway close to junction 25 near Taunton at around 8.30pm last night.
An Avon and Somerset Police spokesman said that the death toll could rise as the recovery operation continued and extensive searches of vehicles and the surrounding carriageway.
Assistant Chief Constable Anthony Bangham described many of the cars as being "burnt literally to the ground".
Patients were taken to nearby hospitals, with the more serious cases being taken to Musgrove Park Hospital.
Injuries range from simple limb fractures to more complex chest and abdominal trauma. A surgeon was flown in by helicopter from Exeter to help treatment efforts.
"None are in a critical condition," said Dr Colin Close, medical director for Musgrove Park.
"Everyone is stable."
Police have called for any witnesses to come forward, especially those with mobile phone or camera footage of the incident.
Further forensic examinations of all the vehicles will take place once they have been removed from the carriageway.
The road is unlikely to re-open until at least Sunday.
A spokesman for Devon and Somerset Fire and Rescue Service described it as "the worst road traffic collision anyone can remember".
Video footage from the scene showed several vehicles engulfed in flames and debris strewn across the road. A number of burning lorries were also on their side.
At least four people who were trapped were cut free by firefighters.
A number of passengers were unable to escape from their burning cars and said crews were faced with a "massive fireball".
"Most vehicles were well alight and most continued to burn for a considerable time," Asst Ch Con Bangham said.
"This made it very difficult to search the vehicles."
He said it was too early to be able to establish what might have caused the accident.
Police are looking into the suggestion that a nearby fireworks display may have caused a momentary distraction to drivers.
One eyewitness reported a number of explosions and black smoke and others said they could feel the heat from the fires while driving on the opposite side of the motorway.
Paul O'Connor was travelling to Plymouth when the incident happened and managed to video dramatic footage of burning cars and lorries.
"I thought it was something to do with bonfire night and then realised it was something quite bad," he told Sky News.
"I have never seen anything like that - I could see people lying on the side of the road. It was quite disturbing really."
Conditions on the road were described as "difficult" at the time of the smash with reports of heavy fog and rain.
Police and 15 fire crews battled the fires and worked to free people from the wreckage on the northbound carriageway.
At least four vehicles were reported to be on fire, including two lorries.
The motorway has been closed in both directions from junctions 23 to 26.
Drivers are advised to avoid the area for the rest of the weekend.
Andrea Day from Trafficlink told Sky News it was the worst accident she has seen in the 10 years she had been working for the traffic information provider.
"I have never come across an accident of this kind - not in terms of the volume of vehicles involved," she said.
Ms Day warned of major disruption over the weekend with delays expected on the A38, the A30 and A303.
In an email sent to Sky News, witness Ciara Neno said: "It was quite frankly the scariest night of my life and we are extremely lucky to be alive tonight.
"A black fog came down very very fast and the Iceland truck in front of us literally disappeared.
"We managed to brake and not hit the truck but the carnage had started and all we heard was 'thump thump thump' and we were waiting to be hit and end up under the lorry.
"I got onto the emergency services and my husband started dragging people from smoking cars. The noise and the smell was horrendous and there was several explosions as the fires took hold."
Jeremy Browne, MP for Taunton Deane, paid tribute to the "bravery" of the emergency workers who dealt with the "horrendous accident".
"There has not been a crash on this scale for many years and the implications of it will be life-changing for many people," he said in a statement.
Chief executive of Musgrove Park Hospital Jo Cubbon said: "Our thoughts are with everyone affected by this tragedy.
"I would like to pay tribute to the staff at Musgrove and all our emergency services partners who have responded with the utmost professionalism in these difficult circumstances."
Anyone concerned about friends or relatives can call an emergency number on 0800 092 0410 .
Police say all other measures should be taken to make contact before this number is dialled.