It happened before midnight on the East Freeway near Sheldon Road.
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The Harris County Sheriff's Office received calls about a man seen without clothes along the freeway, but before deputies arrived, the man was struck and killed, investigators said.
Witnesses told deputies they saw the victim before the crash standing on the side of the freeway and then appeared to get down and crawl. As the witnesses stopped and tried to reverse to approach the man, a black Ford pickup ran over him, investigators said.
The black Ford pickup truck had no tailgate and took off. It appeared the driver was aware that the pedestrian was struck.
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There was no word on the driver's description or the victim's identity.
Several lanes of the freeway were closed while investigators worked to find out who was involved and what may have led to the incident.
Wednesday's crash was the first of at least two fatal pedestrian crashes in Houston in less than eight hours. On Thursday, a pedestrian was struck and killed on the feeder road of North Freeway near Vista Road.