Tracy Hoover, CHP spokeswoman, said the driver of the FedEx truck lost control of the vehicle, crossed over a divider on Interstate 5, side-swiped a car and then smashed head-on into the tour bus around 5:30 p.m. on Thursday.
Apart from the driver, the bus was carrying between 44 and 48 students and three or four chaperones heading to Humboldt State University for a campus tour. The crash took place near the community of Orland, 95 miles north of Sacramento.
The driver of the FedEx truck was killed, said CHP spokeswoman Lacey Heitman. The students were traveling from Los Angeles-area high schools.
Seven students on the bus were among the dead, a local ABC-affiliate reported.
Pictures from the scene showed the bus reduced to a burned-out chassis resting sideways across the highway. Hoover described hunks of twisted metal and broken glass and said flames had roared through the vehicles.
"The big rig and the bus were both engulfed in flames. You are talking about two vehicles that are destroyed. There is hardly anything left of the truck," Hoover said.
Hoover said the injured were taken by air and land ambulances to area hospitals. Shasta Regional Medical Center, which received two patients, said one was in stable condition while the other was undergoing testing and additional treatment.
The condition of the other 30 injured was not immediately known.
"They are traumatized, absolutely. Most of them have scratches, cuts, burns, contusions, and lacerations. A magnitude of injuries," Hoover said.
No one in the car was killed, though the driver was sent to hospital with unspecified injuries, CHP said, though officials could not confirm whether the bus driver was among the dead.
Interstate 5 was closed in both directions and was not expected to reopen until early Friday morning.
Bonnie Kourvelas, a spokeswoman for FedEx Corp, said the company was aware of media reports that one of its trucks was involved in the crash. The condition of the truck's driver, she said, was unknown.
"We are cooperating fully with authorities as they investigate," she said.
Humboldt State University President Rollin Richmond said students from southern California had been traveling to the college campus for a spring preview event on Friday.
"Our hearts go out to those who have been affected, and we are here to support them, and their families, in any way possible," he said in a written statement.
(Reporting by Dan Whitcomb in Los Angeles and Eric Johnson in Seattle; Editing by Alison Williams)
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