Reduced diaphragm contractility has been described in normal subjects after whole body endurance exercise, and it indicates low frequency fatigue (LFF); it is unknown whether LFF is of clinical importance. We therefore studied the effect of treadmill exercise to exhaustion on diaphragm contractility in six patients with severe chronic obstructive pulmonary disease (COPD) (mean FEV1, 0.71, 27% predicted). The subjects first performed a short (control), treadmill walk and then, after resting, a second walk to a state of severe dyspnea. Cervical magnetic stimulation of the phrenic nerve roots was performed at the start of the study and 20 and 30 min after each walk. The twitch transdiaphragmatic pressure (Tw Pdi) was reproducible (mean coefficient of variation, 5.3%; range, 2 to 12.5%). Mean Twi Pdis were 18.4 cm H2O at baseline and 19.6 cm H2O and 19.2 cm H2O 20 and 30 min after the control walk. At the same times after the exhaustive walk, mean Tw Pdis were 19.6 and 20.4 cm H20. Tw Pdi was not reduced by exhaustive treadmill walking (p > 0.9), and a power calculation showed that the study had a 95% chance of detecting a 10% fall at the 5% significance level. We conclude that Tw Pdi is not reduced when patients with severe COPD walk to a state of extreme breathlessness and that therefore low frequency fatigue of the diaphragm does not occur.