Police say the car was heading southbound when it struck the median, overturned and flipped into the northbound lanes.
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The car then struck another car that was northbound.
It happened early Tuesday morning near West 94th Street.
The victims have not been identified.
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The accident is under investigation, but officials believe speed may have been a factor.
The northbound West Side Highway was shut down north of 79th Street as police investigated and crews worked to clear the wreckage.
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