Several people have been killed and as many as 35 injured in a collision involving 27 vehicles on the M5 motorway in Somerset.
An Avon and Somerset Police spokesman confirmed that "some" people have "tragically lost their lives".
There are reports that 10 others have sustained "life changing" injuries.
Some 20 light vehicles and six articulated lorries were involved in the smash on the motorway close to junction 25 near Taunton at around 8.30pm.
At least four people who were trapped have been cut free by firefighters.
Video footage from the scene shows several vehicles engulfed in flames and debris strewn across the road. A number of burning lorries are on their side.
Firefighters can be seen trying to pry open car doors to reach those trapped inside.
One eyewitness reported a number of explosions and black smoke.
The heat of the fires was felt by drivers on the opposite side of the motorway.
A spokesman for Devon and Somerset Fire and Rescue Service described it as "the worst road traffic collision anyone can remember... so many vehicles involved".
Conditions on the road have been described as "difficult" at the time of the smash.
Police and 15 fire crews were battling the fires and working 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 and police say it is likely to remain closed for at least 24 hours.
Chief Inspector Paul Mogg said earlier: "All emergency services are on the scene doing as much as they can to continue the rescue operation and to treat those who are injured.
"There are large tailbacks at present and we would urge all to avoid the area for the next 24 hours at least."
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.
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.