Although it has been postulated that central inhibition of respiratory drive may prevent development of diaphragm fatigue in patients with chronic obstructive pulmonary disease (COPD) during exercise, this premise has not been validated. We evaluated diaphragm electrical activation (EAdi) relative to maximum in 10 patients with moderately severe COPD at rest and during incremental exhaustive bicycle exercise. Flow was measured with a pneumotachograph and volume by integration of flow. EAdi and transdiaphragmatic pressures (Pdi) were measured using an esophageal catheter. End-expiratory lung volume (EELV) was assessed by inspiratory capacity (IC) maneuvers, and maximal voluntary EAdi was obtained during these maneuvers. Minute ventilation (V E) was 12.2 +/- 1.9 L/min (mean +/- SD) at rest, and increased progressively (p < 0.001) to 31.0 +/- 7.8 L/min at end-exercise. EELV increased during exercise (p < 0.001) causing end-inspiratory lung volume to attain 97 +/- 3% of TLC at end-exercise. Pdi at rest was 9.4 +/- 3.2 cm H(2)O and increased during the first two thirds of exercise (p < 0.001) to plateau at about 13 cm H(2)O. EAdi was 24 +/- 6% of voluntary maximal at rest and increased progressively during exercise (p < 0.001) to reach 81 +/- 7% at end-exercise. In conclusion, dynamic hyperinflation during exhaustive exercise in patients with COPD reduces diaphragm pressure-generating capacity, promoting high levels of diaphragm activation.