The Navion B plane crashed into a parking lot between some commercial buildings on the 6900 block of Hayvenhurst Avenue just to the west of the airport.
It crashed around 3 p.m. shortly after departing from Van Nuys Airport, heading to Santa Ynez Airport, according to the FAA.
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The Los Angeles Fire Department was on scene to put out the fire from the wreckage.
2 killed in single-engine plane crash near Van Nuys Airport
There were no reports of anyone on the ground being injured.
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The Federal Aviation Administration and National Transportation Safety Board will investigate the cause of the crash.