Caltrans spokeswoman Terri Kasinga says the crash occurred shortly after 2 a.m. Wednesday just west of Blythe when a big rig traveling east jackknifed onto the median and spilled a load of steel pipes into all lanes.
She says the bus either swerved to avoid the pipes or struck them and overturned onto the shoulder and slid 50 feet down a slight embankment. The bus was traveling from Phoenix to Los Angeles.
Kasinga says four people are dead but there could be more fatalities.
Emergency helicopters have transported several passengers with critical injuries.
Kasinga says all lanes of the interstate will be closed for several hours.