California Highway Patrol officers say a car and a semi-truck collided just before 8:30 pm on northbound Highway 99 near Tulare Street.
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The car caught fire, and the two people inside died.
The semi-truck driver was not injured in the crash.
CHP officers are working to determine what caused the two vehicles to collide.
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One lane of northbound Highway 99 was closed for the investigation but has since reopened.