The crash was reported at about 8:45 a.m. and blocked three lanes inbound at Fondren Road. All lanes have since reopened.
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Authorities said a 20-year-old man in a blue Kawasaki motorcycle was northbound on the freeway, riding between two right lanes. That's when police said he crashed into the back of a black Honda Civic and a gray Jeep Cherokee.
HPD said the motorcyclist flew off his bike and hit a white Toyota Corolla. Paramedics transported the victim to the hospital, where he was pronounced dead.
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Police said two other people involved in the crash were taken to the hospital for back pain.
Hours later, on Tuesday, a second motorcyclist died in a two-vehicle crash along the East Freeway. That victim has not yet been identified.
READ MORE: All mainlanes of East Freeway WB at Federal blocked after 2nd motorcyclist killed in crash today