R habdomyolysis and myoglobinuria occur commonly in men who sustain environmental heat injury during intensive physical training in hot climates. These also occur in patients with potassium depletion. Since physical training in hot climates may be accompanied by serious losses of body potassium, the possibility was considered that performance of strenuous exercise when potassium deficient might enhance susceptibility to rhabdomyolysis.Potassium is released from contracting skeletal muscle fibers and its rising concentration in interstitial fluid is thought to dilate arterioles thereby mediating the normal rise of muscle blood flow during exercise. If potassium release from deficient muscle were subnormal, exercise would not be accompanied by sufficient muscle blood flow and rhabdomyolysis could occur by ischemia.This hypothesis was examined by comparing the effect of electrically stimulated exercise on muscle blood flow, potassium release, and histology of the intact gracilis muscle preparation in normal and potassium-depleted dogs. In normal dogs, muscle blood flow and potassium release rose sharply during exercise. In contrast, muscle blood flow and potassium release were markedly subnormal in depleted dogs despite brisk muscle contractions. Although minor histologic changes were sometimes observed in nonexercised potassium-depleted muscle, frank rhabdomyolysis occurred in each potassium-depleted animal after exercise.These findings support the hypothesis that ischemia may be the mechanism of rhabdomyolysis with exercise in potassium depletion.