Sickle cell trait, which affects approximately 8% of American blacks, is generally felt to be a benign condition. Exercise-related collapse in persons with sickle cell trait is a rare but serious complication. It occurs most often in military recruits and deconditioned athletes undergoing intense physical training, but can also occur in other situations in which an individual exerts himself beyond his limits of endurance. Local hypoxia causes intravascular sickling, in turn causing vascular occlusion and organ and tissue damage. This can result in rhabdomyolysis, myocardial ischemia, arrhythmias and sudden death. Risk factors include poor physical conditioning, inadequate hydration, excess heat and/or altitude, heat-retaining clothing and febrile illness. Seven cases are presented, and the implications of the diagnosis of sickle trait-associated collapse and sudden death are discussed.