The crash happened around 11 pm near H Street and Inyo Avenue.
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Tulare police say a sedan driving south on H Street stopped at the stop sign and then entered the intersection.
That's when an SUV heading east on Inyo struck the sedan, causing it to flip over and land on its side.
Both people inside of the sedan were killed in the crash.
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The driver of the SUV was taken to the hospital.
Authorities say he is cooperating with their ongoing investigation.
It is not yet known if alcohol or drugs were a factor.