The effects of the administration of 100% oxygen on minute ventilation () and arterial blood gases were studied in patients with chronic obstructive pulmonary disease during acute respiratory failure. The administration of O₂ resulted in an early decrease in , which averaged 18% ± 2 SE of the control , and was due to a decrease in both tidal volume (Vt) and respiratory frequency (f). This was followed by a slow increase in , such that after 15 min of breathing O₂, rose to 93 ± 6% of the control room air value, with both Vt and f similar to control values. Despite the small difference between while breathing room air and that at the fifteenth minute of O₂ inhalation, Pa_CO2 increased by 23 ± 5 mmHg, and no significant correlation was found between the changes in and Pa_CO2. By the fifteenth minute of O₂ inhalation the Pa_O2 averaged 225 ± 23 mmHg, and it was concluded that despite the removal of the hypoxic stimulus of O₂ inhalation, the activity of the respiratory muscles remained great enough to maintain at nearly the same degree as that while breathing room air. Consequently, the changes in Pa_CO2 after the administration of O₂ were mainly due to increased inhomogeneity of distribution within the lungs.