The collision occurred about 11:30 p.m. on Victory Boulevard near Mason Avenue, according to the Los Angeles Police Department.
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One man died at the scene and the other man died at a hospital, an LAPD spokesperson said.
Information was not immediately available on the identities of the fatally injured men, who apparently were in their 20s, police said.
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According to police, one vehicle was eastbound on Victory Boulevard when it crossed into the westbound lanes and collided with the other vehicle.
The cause of the crash is under investigation.
City News Service contributed to this report.