Sixteen healthy males volunteered to perform both an incremental maximal and prolonged submaximal treadmill test with beta-blockade (2 X 80 mg oral propranolol per day) or matched placebo in a blind crossover design. Prior to and following the prolonged exercise, electrical stimulation of the triceps surae was performed to examine contractile properties. During the maximal test, the heart rate (HR) was reduced at all times by beta-blockade. The time to exhaustion in this test was significantly reduced by beta-blockade (P less than 0.03), while the maximal oxygen uptake (VO2 max) was not significantly lower (P = 0.06). In response to prolonged treadmill walking at 60% of VO2 max, the HR was reduced but VO2, respiratory quotient and ventilation were not affected by beta-blockade relative to placebo. Plasma concentrations of free fatty acids increased during exercise in the placebo but not beta-blocked treatment (P less than 0.0001). Plasma noradrenalin and adrenalin increased with exercise; the increase in adrenalin with beta-blockade was greater than that with placebo (P less than 0.0001). The RPE obtained at intervals during the prolonged exercise were greater for beta-blockades than placebo. Eight of 16 subjects were unable to complete full 90 min with beta-blockade; but all 16 completed the test with placebo. The electrically evoked twitches in the triceps surae muscle group after exercise did not differ in peak torque or one-half relaxation time compared to pre-exercise. The time to peak twitch torque was significantly shorter after exercise. No differences in twitch were observed due to beta-blockade. The tetanic responses at 10, 20, 50 and 100 Hz were not affected by either exercise or the beta-blockade. In conclusion, an increased subjective estimate of fatigue (RPE) was observed during prolonged exercise with beta-blockade. This subjective fatigue did not relate to altered peripheral muscle force production during electrical stimulation. The results suggest either a central rather than peripheral origin of fatigue, or fatigue in a muscle group not examined by stimulation of the triceps surae.