Drunk driving appears to be a factor in the crash that happened along Route 12 in Volo just after 8 p.m.
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Sheriff's investigators said a man was driving a Ford Mustang in the wrong direction when he hit a Mitsubishi SUV head-on.
"The Ford driven by a 24-year-old man of Ingleside, was northbound in the southbound lanes of traffic," said Lake County Sheriff's Office Spokesperson Christopher Covelli.
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Investigators said an open container of alcohol was found inside the Mustang that was going in the wrong direction.
"Investigators do believe impairment was a factor for the driver of the Ford," Covelli said.
Karen Ocampo and her brother, Jesus Vilchis, passed the wrong-way driver moments before the crash.
"I saw a Mustang in the opposite direction, the same lane as me, coming the opposite way," Vilchis said.
"I saw the Mustang coming our way, the lights, I was just like, 'What's going on?'" Ocampo said.
Both vehicles were barely identifiable after the head-on collision.
Paramedics rushed three people to local hospitals.
The Ford's driver and the Mitsubishi's driver, a 36-year-old Deerfield woman, suffered serious injuries. A front-seat passenger in the Ford, a 23-year-old man, was also injured.
Authorities have not released their names, but they said the Deerfield woman was apparently the most seriously injured. All three of those injured remained hospitalized on Monday afternoon.
The spokesperson said investigators still need to collect evidence, including medical records, before they determine whether to file charges.