Three children have died and two women are seriously injured after a crash on the M6 between junctions 14 and 15, the West Midlands Ambulance Service has said.
The accident happened on the northbound carriageway between junctions 14, near Stafford, and 15, near Stoke-on-Trent.
The two women have been taken to University Hospital of North Staffordshire and are in a "stable" condition, said a hospital spokesman.
Next of kin are being informed.
Accident and recovery work is under way and the stretch of M6 is expected to remain shut for several hours.
The accident happened shortly before 1200 GMT.
Staffordshire Police initially said "several vehicles" had been involved, causing "multiple fatalities", but later said it was a one-vehicle crash. No further details on the number of dead have been released.
In a statement, Staffordshire Police advised motorists to avoid the M6 between junctions 14 and 15 because the motorway would remain closed in both directions until late afternoon.t said: "At this early stage police are not yet able to confirm details but are confirming that there have been lives lost.
"The incident took place northbound just before junction 15 exit road and involved one vehicle."
The M6 is among a number of key routes that have been struck by weather-related delays in recent days amid heavy rain.