We have recently shown that patients with chronic obstructive pulmonary disease (COPD) develop contractile fatigue of their quadriceps muscle following endurance exercise. Pulmonary rehabilitation can produce physiological adaptations in patients with COPD. We hypothesized that if pulmonary rehabilitation induces physiological adaptations in the exercising muscle, it should become more fatigue resistant. Twenty one patients with COPD, mean age 69.9 +/- 1.9 yr, FEV(1) 45 +/- 4% predicted, participated in an 8-wk outpatient, supervised pulmonary rehabilitation exercise program. Quadriceps contractile fatigue was detected by a fall in quadriceps twitch force postexercise. Twitch force was measured during magnetic stimulation of the femoral nerve. Because potentiated twitches may be more sensitive at detecting fatigue, both unpotentiated (TwQu) and potentiated (TwQp) twitches were obtained before and 10, 30, and 60 min after constant load cycle exercise. Prerehabilitation, during constant load exercise, patients exercised at 37 +/- 4 W for 11.2 +/- 1.8 min. Prerehabilitation, TwQu fell significantly postexercise down to a minimum value of 82.5 +/- 3.1% of the baseline preexercise value (p < 0.001). Similarly, prerehabilitation, TwQp fell significantly postexercise down to a minimum value of 73.9 +/- 3.9% of baseline (p < 0.001). Postrehabilitation, for the same intensity and duration of exercise, TwQu was not significantly different from baseline at any time postexercise. Postrehabilitation, TwQp fell significantly postexercise but the fall in TwQp with exercise was significantly less postrehabilitation compared with prerehabilitation (p < 0.001). In conclusion, pulmonary rehabilitation resulted in increased fatigue resistance of the quadriceps muscle in patients with COPD.