Crews were called around 2:30 am on Thursday to Anna and Church Avenues.
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When they arrived, they found flames coming from two trailers filled with tires.
Firefighters had to cut a fence to enter the grounds. The storage yard was filled with old vehicles, boats and car parts.
Officials said burning tires are tough to put out.
"It is a challenge for us. Not only a lot of water, but it puts off a lot of really bad smoke with chemicals, so our firefighters really have to make sure they're on breathing apparatus the whole entire time," said Fresno Fire Battalion Chief Tim Fulmer.
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The smoke and flames could be seen along Highway 99.
An investigator is working to determine what caused the fire. No one was hurt.