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Background: Rhabdomyolysis is a syndrome characterized by muscle necrosis that leads to release of the intracellular contents of muscle cells into the systemic circulation. Rhabdomyolysis due to overexertion is an uncommon but well-known severe complication of strenuous activity. Exertional rhabdomyolysis (ER) is typically described in weight lifters and military recruits undergoing basic training. Few cases have been reported in football players without known predisposing risk factors. We report our experience with this condition in college football players in a single institution. Materials and methods: College football players hospitalized for heat illness complicated by rhabdomyolysis were identified over a 23-year period. Clinical and laboratory findings were collected. Clinical course was recorded. Results: Twelve patients were identified. All were Black males. One had sickle cell trait. BMI averaged 33 kg/m2 (range 23-45 kg/m2). Peak creatine phosphokinase (CPK) averaged 14,850 IU/L (range 1,021-109,616 IU/L). Serum creatinine averaged 1.9 mg/dl (range 1.2-3.1 mg/dl). Ten of twelve cases occurred in August. All responded to intravenous hydration with normalization of CPK and renal function. All returned to football. Conclusions: ER is a serious complication of strenuous physical activity that can threaten renal function. ER tends to occur in August, which coincides with the start of football practice when athletes are more likely to be detrained. The condition can occur in Black athletes in the absence of sickle cell trait. ER carries a good prognosis when recognized early and treated adequately. [ABSTRACT FROM AUTHOR]