Respiratory muscle fatigue (RMF) occurs during heavy exercise in humans. N-acetylcysteine (NAC) infusion has been shown to reduce RMF, suggesting that oxidative stress is a contributing factor. The purpose of the present study was to determine the effect of an acute oral dose of NAC on RMF during heavy exercise. Subjects (n=8) were given either placebo (PLA) or NAC (1,800 mg) 45 min prior to a 30 min constant load (85V(O)(2peak)), discontinuous exercise test. Maximum respiratory pressures (inspiratory, PI(max); expiratory, PE(max)) and venous blood samples were made prior to and following each 5 min of exercise. There was no difference (p>0.05) in PI(max) between NAC (127.9+/-34.1 cm H(2)O) or PLA (134.1+/-28.1cm H(2)O) at rest. During exercise, PI(max) was significantly lower with PLA ( approximately 14%) compared to NAC at 25 and 30 min suggesting less RMF with NAC. There were no differences (p>0.05) between groups in PE(max), V(O)(2), V(E), or heart rate at rest or throughout exercise. These results suggest that an acute dose of NAC reduces RMF during heavy exercise.