It happened just after 8 p.m. on the 400 block of North Washington Street near Butler Avenue.
In addition to the four fatalities, Pottstown Borough Manager Justin Keller confirmed two people were hospitalized for unknown injuries and two others may still be missing.
Debris could be seen scattered across the neighborhood after the blast leveled at least one home.
Residents tell Action News they heard a blast and then reported seeing a fire.
Christian Gonzalez says he thought it was thunder at first.
“I really thought it was really loud thunder just nearby, but it shook the area,” he said.
Police have not identified the victims at this time.
There was no immediate word on what caused the explosion.
Keller said residents that need assistance should come to the Pottstown Senior High School.
All schools in the district are canceled on Friday.
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