The California Highway Patrol says it was just before 2 a.m. when 37-year-old David Barajas was driving a Ford F-250 in the No.1 lane eastbound on Highway 198.
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Officers say at the same time, 63-year-old Steven Mahoney was driving a Kia Soul in the No. 2 lane.
An unidentified 24-year-old man driving a Toyota Corolla drove the wrong way towards Barajas and Mahoney.
The driver of the Toyota crashed head-on with Barajas, his car then went up in flames. He died at the scene.
Barajas's Ford then overturned, landing in front of Mahoney's Kia resulting in another crash.
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In the Ford, Barajas was airlifted to the hospital while his two passengers, who were also injured, were taken to the hospital by ambulance.
In the Kia, Mahoney and his passenger suffered minor injuries and were also taken to the hospital.
Officers say at this time, it's unknown if alcohol or drugs played a factor in the crash.
Stay with ABC30 for the latest details on this developing story.