Officers from the California Highway Patrol responded at 2:55 a.m. to the northbound 101 Freeway and Los Angeles Street, the site of the collision, the CHP said.
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The victim was struck by a vehicle in the No. 3 lane of the northbound freeway. The driver of that vehicle stayed at the scene and cooperated with authorities.
The woman was pronounced dead at the scene. Investigators have not yet released her name.
It was not immediately known how the woman fell from the party bus, and if alcohol was involved.
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The CHP's Central Los Angeles office urged anyone with information about the death to call them at (323) 343-0732.