A white Chevy Traverse was driving north at a high rate of speed just after 2:30 a.m. in the 1000-block of North Cicero Avenue, when it rear-ended an Acura MDX, CPD said.
The impact caused the Acura to crash and then become engulfed in flames, police said.
The man driving the Acura was pronounced deceased by Chicago fire officials on the scene.
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The man driving the Chevy was taken to Mt. Sinai hospital in good condition, and will be issued traffic citations, CPD said.
Major accidents is on the scene investigating.
Neither man was immediately identified.