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It happened around 4 p.m. in Mooreville off County Road 1310 near Highway 178.
Lee County Sheriff Jim Johnson says the 21-year-old motorcyclist, who was wearing his helmet, was flown to North Mississippi Medical Center in Tupelo.
According to Lee County Coroner Carolyn Green, the man died in the hospital's emergency room from multiple trauma. On Friday, Green identified the victim as 20-year-old Blake Whitworth of Mooreville.
The woman driving the car was not hurt.
Johnson says his department will be at the site of the crash Friday to reconstruct the accident to determine what caused it.