Inbound train 302 hit a vehicle near 115th Street and Marshfield Avenue about 7:25 a.m. in Chicago's Morgan Park neighborhood, Metra said.
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The westbound vehicle had reportedly gone around the crossing gates, Metra said.
Chicago fire officials said the female driver of the vehicle was taken to Christ Hospital in critical condition, and three passengers were taken to Little Company of Mary Medical Center in good condition.
The tracks reopened about 8:45 a.m., but Metra said some delays on the Rock Island Line remained.
Trains used the Beverly Branch until the tracks were cleared.
The train involved in the incident also sustained some minor damage.