The heterozygous condition characterized by the presence of hemoglobin AS (sickle-cell trait) occurs in approximately 8 percent of the American black population. Unlike the homozygous state (sickle-cell disease), sickle-cell trait is not widely recognized as a cause of life-threatening illness or death despite over 30 case reports that describe fatal or serious complications of exercise in young black males with this condition. These reports identify heat stress, dehydration, viral illness, and poor physical conditioning as factors that may contribute to exertional rhabdomyolysis and sudden death, suggesting multifactorial etiology; however, since sickling is known to occur postmortem, it remains controversial as to whether the pathogenesis of these exercise-related deaths involve microvascular obstruction by sickled erythrocytes. The authors describe three young black individuals with no significant past medical history who died following physical exertion. In all three cases, postmortem hemoglobin electrophoresis demonstrated hemoglobin AS. In none of the cases was the body temperature found to be elevated. These cases should remind the forensic community that, in the proper setting, sickle-cell trait must be viewed as a potentially fatal disorder. 3 figures and 10 references