Investigators found a 38-year-old Green Bay man had been driving the wrong way, entering the highway coming down the STH 57 off ramp and causing the vehicles to crash head-on.
The 38-year-old man hit a car with four people inside. The two passengers in the backseat, a 56-year-old woman and an 84-year-old woman both from the Appleton area, were pronounced dead at the scene, according to deputies.
The driver of the vehicle and the front seat passenger were both brought to Aurora Hospital with critical injuries. All four people were related, deputies said.
The 38-year-old Green Bay man was brought to Aurora Hospital via Eagle III and pronounced dead at the hospital.
The highway is still shut down as the Brown County Sheriff's Office Accident Reconstruction Team investigates.
The names of those involved will be released Sunday, the sheriff's office said.