The effects of reserpine upon skeletal muscle and blood lactate levels have been studied in exercised and control rats. The exercise program consisted of 12 weeks of running on a motor-driven treadmill at 26.8 m/min for 1 h per day, 5 days per week. Animals received reserpine doses of 2.5, 5.0, and 12.5 mg/kg (i.p.) 24 h prior to sacrifice. Skeletal muscle and blood lactate levels were measured from animals sacrificed at rest or immediately after a fatiguing run. Tissue lactate levels were elevated only in those animals receiving 2.5 mg/kg of reserpine and exhaustive exercise. Blood lactate levels were unaffected by the drug and by the run to exhaustion. The results indicate that elevated muscle lactate levels are not the sole cause of muscular fatigue.