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A motorist in a red Chevrolet Silverado was headed south in the northbound lane of Route 33 when they drove up an on-ramp from Route 22, troopers said.
Three vehicles were involved and authorities were called around 10:40 a.m.
One victim was pronounced dead at the scene and two others were taken to area hospitals in unknown condition.
The deceased victim's name was not released.
"Currently, all traffic on State Route 22 Eastbound is being detoured on State Route 33 Southbound, and traffic is unable to exit from State Route 33 Southbound to State Route 22 Eastbound," state police said.
Anyone who witnessed the Chevy driver heading the wrong way, or anyone who has video of the incident, is being asked to call PSP's Bethlehem Station at 610-861-2026.
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