Denton police spokesman Orlando Hinojosa says the accident occurred sometime before 6:30 a.m. Saturday on Interstate 35.
Hinojosa says one of those killed was a 55-year-old woman whose vehicle was struck by another that was traveling south in a northbound lane.
The driver of the wrong-way vehicle, a 25-year-old man, also died, and two other motorists received minor injuries, the spokesman said.
The highway's northbound lanes were shut down for four hours as a result of the accident.
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