The purpose of this study was to determine whether supplemental oxygen-induced decreases in ventilation (VE) and mouth occlusion pressure (P0.1) in patients with COPD are related to the ventilatory or P0.1 responses to hypoxia (delta VE/delta SaO2, delta P0.1/delta SaO2). We measured these responses in 14 patients with a (mean +/- SD) FEV1 of 0.95 +/- .41 L. The VE and P0.1 were also measured while the patients sequentially breathed either room air or supplemental oxygen (1-2 L/min) for 10 min in a randomized single blind fashion. The mean (+/- SEM) SaO2 increased from 90.8 +/- 0.99 percent to 95.2 +/- 0.46 percent and the VE decreased during oxygen breathing from 12.3 +/- 0.46 to 11.6 +/- 0.47 L/min (p < 0.03). However, the individual changes in VE were not significantly related to the corresponding changes in SaO2 (CHG SaO2), (delta VE/delta SaO2), or (delta VE/SaO2) (CHG SaO2). Similarly, the P0.1 decreased from 2.50 +/- 0.27 to 2.26 +/- 0.20 cm H2O (p < 0.05), but the individual changes in P0.1 were not significantly related to (CHG SaO2), (delta P0.1/delta SaO2), or (delta PO.1/delta SaO2) (CHG SaO2).