Sickle cell trait has been associated with an unexplained increased risk of sudden death during military basic training. Previous studies of cardiopulmonary function in persons with sickle cell trait at sea level or after brief exposure to moderately high altitude have not shown significant abnormalities. To determine whether cardiopulmonary function is impaired in men with sickle cell trait who chronically reside at moderately high altitude, we prospectively studied 17 men with sickle cell trait and 25 men with normal hemoglobin. All subjects had resided at > or = 1609 m above sea level for at least 10 years. Resting pulmonary function and cardiopulmonary performance during exercise to exhaustion were evaluated. No statistically significant differences were observed between subjects with sickle cell trait and controls for any of the resting pulmonary function variables measured. All parameters of exercise performance were not statistically different between the groups. Increasing age was associated with a similar decrease in work capacity and oxygen consumption in both groups. Electrocardiogram findings were not statistically different between groups. We conclude that chronic exposure to moderately high altitude does not impair cardiopulmonary function in men with sickle cell trait.