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The fire started about 1 p.m. in the back of the building, which is just off of US 70.
The warehouse used to be an old seafood restaurant but later became a storage space to sell appliances.
For most of the afternoon, firefighters had a tough time getting to fire because of the smoke.
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"I've heard of fires in the winter but this is pretty incredible," said Marlene Slieter, a neighbor. "It's been going forever. When I first moved to Durham in 2000 it was still a restaurant and shortly after that, no more. And it's just been sitting here."
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The owner of the building discovered the fire and called 911, according to ABC11's Tim Pulliam.
Firefighters said the stoves and refrigerators packed inside the building fueled the blaze.
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The cause of the fire has not yet been determined. The fire marshal and the SBI are being called to investigate.
No injuries have been reported.