Three helicopters have been scrambled after a “serious collision” involving two lorries and a minibus on the M4 in Berkshire.
The incident took place between junction 14 at Hungerford and 13 at Chieveley.
South Central Ambulance Service said three people have been rushed to hospitals in Oxford and Bristol with life-threatening injuries.
The crash has been described by witnesses as being the "worst they have ever seen".
Thames Valley Police tweeted: "Officers have closed part of the M4 in Berkshire following a serious collision.
"The eastbound carriageway between Junction 14 at Hungerford and 13 at Chieveley is likely to remain closed for several hours.
"Please avoid the area and take alternative routes."
Motorist James Lloyd advised others to avoid the area.
"M4 closed due to worst accident I’ve ever seen in many years of driving. Avoid area and if you’re caught in the tail back be patient," he tweeted.
"I promise you don’t want to get past it until emergency services are finished."
