In 20 patients with chronic hypoxemia due to chronic obstructive pulmonary disease, we measured responses to CO2 and hypoxia in terms of ventilation and P0.1, the pressure generated by the respiratory muscles during the first 0.1 s of inspiratory effort against a closed airway at functional residual capacity. These responses were compared to those of a control group of 17 patients with similar ventilatory abnormality but without hypoxemia. Hypoxemic patients demonstrated significantly less response to hypoxia than did control subjects in terms of both ventilation and P0.1 The decreased hypoxic response might be analogous to that reported in high altitude dwellers and patients with cyanotic congenital heart disease. Ventilatory responses to CO2 were depressed in hypoxemic patients, but P0.1 responses were not significantly decreased. While breathing at rest with arterial O2 saturation of 95 per cent, hypoxemic patients demonstrated the same minute ventilation as control subjects, but tidal volume was smaller, inspiratory duration was shorter, and breathing frequency was slightly higher. This breathing pattern appeared to be independent of whether or not these patients retained CO2.