The flames began at about 4:15 a.m. at a home on the 400 block of Hale Street.
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Fire crews first responded to reports of a vacant house on fire. The fire then extended to the home next door.
"I saw the orange glow coming through my door. I jumped up and I looked at the door and the whole house was engulfed with flames. I called 911," said Johnny Corson, who lives nearby.
Video from Chopper 6 showed both homes were no longer standing and had been reduced to rubble.
Water supply issues hampered firefighters' attempts to extinguish the blaze, sources said.
No injuries were reported in the fire.
Both homes were vacant because they were impacted by a nearby house explosion in May 2022 that killed five people.
Neighbors say Tuesday's fire is a reminder of the devastation.
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Officials ID 5 killed in Pottstown explosion; most were children
"I don't know, it's weird. I don't know how much more this neighborhood can endure," said Corson.
The Pottstown fire chief said he wanted to assure residents the fire is not connected to the explosion.
"It's a circumstance of nature, another fire. There's nothing that leads us to believe that this has anything to do with the explosion," said Chief Frank Hand.
The cause of the fire is under investigation.