It happened around 11 p.m. near Millerton and Winchell Cove roads near Table Mountain Casino.
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The California Highway Patrol says a sedan was traveling eastbound on Millerton when a man on a motorcycle traveling westbound on the same road moved in front of the sedan.
The motorcycle and sedan hit head on and the motorcyclist was ejected.
Officers say the man died at the scene.
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The two people in the sedan were taken to Community Regional Medical Center with minor injuries.
The roads were closed for several hours as officers cleared the scene.
it is unknown if alcohol or drugs were factors in the crash.