According to Franklin County dispatchers, the call came in around 2:27 p.m., near mile marker 3.
According to PennDOT, all lanes of I-81 southbound in Franklin County were shut down for hours as crews worked to tow the vehicles off of the roadway, and clear debris.
Drivers experienced heavy traffic along I-81, as well as Rt. 11 due to the accident.
Officials say two people were taken to Meritus Medical Center in Hagerstown, Maryland for minor injuries.
No word on what caused crash, or if slippery conditions played a factor.
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