Dynamic hyperinflation contributes to exertional breathlessness and reduced exercise tolerance in chronic obstructive pulmonary disease (COPD) patients. This study examined whether oxygen supplementation results in a dose-dependent decrease in hyperinflation associated with functional and symptomatic improvement. Ten severe COPD patients without clinically significant oxygen (O2) desaturation during exercise, and seven healthy subjects, performed five exercise tests at 75% of maximally tolerated work rate. Inspired oxygen fraction (FI,O2) was varied (0.21, 0.3, 0.5, 0.75 and 1.0) among tests in a randomized order. Ventilation (V'E) was measured, and end-inspiratory (EILV) and end-expiratory (EELV) lung volume changes were assessed from inspiratory capacity manoeuvres. In the patients, compared to room air, endurance time increased with FI,O2=0.3 (mean+/-SEM 92+/-20%) and increased further with FI,O2=0.5 (157+/-30%). At isotime, compared to room air, there were significant reductions in dyspnoea score, EELV, EILV, V'E and respiratory frequency (fR) with FI,O2=0.3. Improved endurance time negatively correlated with change in EELV (r=0.48, p=0.002) and EILV (r=0.43, p=0.005). The dyspnoea rating decrease correlated with fR decrease. In healthy subjects, smaller V'E and fR decreases were observed at FI,O2=0.5, accompanied by more modestly increased endurance. Oxygen supplementation during exercise induced dose-dependent improvement in endurance and symptom perception in nonhypoxaemic chronic obstructive pulmonary disease patients, which may be partly related to decreased hyperinflation and slower breathing pattern. This effect is maximized at an inspired oxygen fraction of 0.5.