It happened at 8:45 a.m. Friday in the 2200 block of Swamp Pike.
Images from Chopper 6 HD showed extensive damage to a sedan, an SUV and a minivan, with debris spread across the divided highway.
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A second minivan was parked nearby. Numerous fire and rescue vehicles were on the scene.
Action News is told five people have been taken to area hospitals, one airlifted by a medical helicopter.
There was no immediate word on the extent of injuries or what led to the crash.