It happened before 3:00 p.m. Wednesday on West Ridge Pike at Airport Road.
Police say at least two vehicles collided.
One victim suffered serious injuries. That person was airlifted to Hahnemann Hospital in Philadelphia.
Two other people were taken by ground to Pottstown Hospital. A fourth was taken to West Reading Hospital.
Motorists were being asked to seek alternative routes as medics tended to the injured and crews worked to clear the scene.