Airway resistance decreases when hypoxemic subjects with chronic obstructive pulmonary disease (COPD) breathe 30% O2. To verify this finding and to localize the site of action of O2, flow-volume curves on air and helium-O2 mixtures were obtained before and after subjects breathed 30% O2. Patients with COPD and hypoxemia showed an increase in flow rates and a decrease in the density dependence of flow while breathing 30% O2. Atropine produced a similar change in flow rates and density dependence, but then no further change occurred with 30% O2. Five control subjects with COPD, who performed the same sequence of tests without breathing 30% O2, showed no change in flow rates or density dependence. Normal control subjects also showed no change in flow rates or density dependence while breathing 30% O2. Breathing 30% O2, relieves hypoxia-induced bronchoconstriction and appears to act on large airways.