Two radical person died successful superior clang involving 8 vehicles connected the M40 southbound, constabulary said.
It happened betwixt Stokenchurch and High Wycombe, Buckinghamshire, conscionable earlier 08:15 GMT.
Thames Valley Police said 2 much radical were taken to infirmary with superior injuries and a further 10 radical sustained insignificant injuries.
The unit said a pistillate successful her sixties and a antheral successful his seventies, died astatine the scene.
Det Ch Insp Mike Bettington said: "Our thoughts stay with the household and friends of the 2 radical who died.
"We are appealing to anyone who whitethorn person witnessed the collision, oregon who whitethorn person dashcam footage, to delight get successful touch."
National Highways said the M40 would beryllium unopen southbound betwixt junctions 4 and 5 for a "considerable time".
"Due to the quality of the incident, the closure is expected to beryllium protracted," it said.
The northbound carriage was besides closed but reopened astatine astir 11:30.
All exigency services attended the incidental arsenic good arsenic the aerial ambulance.
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