Patients with chronic obstructive pulmonary disease (COPD) are at a mechanical disadvantage and should be predisposed to the development of diaphragmatic fatigue when the ventilatory system is stressed by exercise. The purpose of this study was to determine whether patients with moderately severe COPD develop contractile fatigue of the diaphragm after cycle exercise to the limits of tolerance. Twelve male patients with COPD, age 61.4 +/- 3.0 yr, participated. Their forced expiratory volume in 1 s (FEV(1)) was 1.79 +/- 0.14 L, 49.6 +/- 3.4% of predicted. Patients cycled at 60-70% of their predetermined maximal work capacity until they had to stop because of intolerable symptoms. Twitch transdiaphragmatic pressure (Pdi,tw) was measured during cervical magnetic stimulation before and 10, 30, and 60 min after exercise. A persistent fall in Pdi,tw postexercise of >/= 10% was considered potentially indicative of contractile fatigue of the diaphragm. Patients cycled for 10.2 +/- 2.0 min at a workload of 59.9 +/- 4.3 W. Patients exercised maximally relative to their capacity reaching a peak oxygen consumption (V O(2)) of 108.1 +/- 2.8% of the peak V O(2) obtained during a preliminary maximal incremental exercise test. Pdi,tw was not significantly different from baseline at any time postexercise. Pdi,tw was 19.9 +/- 1.6 cm H(2)O at baseline, 19.6 +/- 2.0 cm H(2)O at 10 min postexercise, 18. 6 +/- 2.0 cm H(2)O at 30 min postexercise, and 19.5 +/- 1.7 cm H(2)O at 60 min postexercise. In the individual patients, two of the patients had a persistent >/= 10% fall in Pdi,tw postexercise, potentially indicative of contractile fatigue of the diaphragm. In conclusion, the majority of patients with moderately severe COPD do not develop contractile fatigue of the diaphragm after high-intensity constant workload cycle exercise to the limits of tolerance.