The crash happened just before 6 pm on Avenue 368 and Road 80.
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The California Highway Patrol says a Ford Mustang traveling south on Road 80 lost control of the vehicle and swerved into a Chevy Silverado.
The Ford driver and two passengers were taken to the hospital with major injuries.
Officials say they were not wearing seatbelts.
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The Chevy driver was also hospitalized.
The cause of the crash remains under investigation.