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"My fans have been waiting long enough," Mayweather tweeted. "Floyd Mayweather vs Victor Ortiz. Sept-17 2011 for the WBC World Championship."
Mayweather, 41-0 with 25 knockouts, has not fought since a unanimous decision over Shane Mosley on May 1, 2010.
"At this stage of my career, these are the challenges I look for, a young, strong, rising star looking to make his mark in boxing by beating me," the unbeaten Mayweather said in a statement.
"Ortiz is just going to be another casualty, the 42nd one who tried and failed."
(Reporting by Gene Cherry in Raleigh; Editing by Julian Linden)
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