The excessive load placed on inspiratory muscles when patients with COPD exercise could lead to fatigue and contribute to exercise limitation. Slowing of maximal relaxation rate (MRR) of skeletal muscle is an early index of the fatiguing process. We investigated whether inspiratory muscle MRR slows when patients with COPD walk to exhaustion. We studied nine well-trained and motivated patients with stable severe COPD (mean FEV1: 0.7 L, 28% predicted). Each subject performed sniff maneuvers before and after walking on a treadmill until they were forced to stop because of dyspnea. Esophageal (Pes), gastric, and transdiaphragmatic pressures were measured using balloon-tipped catheters. MRR was calculated as the percent Pes drop/10 ms. In the first minute after exercise there was a mean decrease of Pes MRR of 42% (range, 21 to 65%) (p < 0.01), which returned to baseline within 3 to 5 min. The fall in MRR indicates that the inspiratory muscles of patients with COPD walking to exhaustion are sufficiently heavily loaded to initiate the fatiguing process.