The State Highway Patrol's statement says the crash happened Tuesday morning on State Route 48 in Warren County's Clearcreek Township, about 40 miles (64 kilometers) north of Cincinnati.
The patrol's Lebanon post says 16-year-old Thomas Williamitis, of Oregonia, was traveling northbound and died at the scene. The driver of one of the southbound vehicles was hospitalized with life-threatening injuries, while the other driver had minor injuries.
Troopers say a fourth vehicle was struck by crash debris, but that driver wasn't injured.
The patrol says alcohol and drugs do not appear to be factors in the crash that remains under investigation.
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