During CO2 rebreathing, we measured the pressures generated at the mouth and in the esophagus during the first 0.1 sec of inspiratory effort against a closed airway in 6 normal subjects and 6 patients with chronic obstructive lung disease. Normal subjects showed similar reponses to CO2 in terms of both mouth pressure and esophageal pressure. Patients' responses at the mouth to CO2 were decreased compared to those of normal subjects, but the responses in the esophagus were not significantly different. The patients demonstrated a greater response of occlusion pressure measured in the esophagus than at the mouth. In patients with altered mechanical properties of the lung, the change in mouth occlusion pressure might be influenced by problems of equalization of pressure within the airways due to unequal time constants, by problems of regional differences in pressure gradients over the pleural surface, or both. Esophageal pressure during airway occlusion 100 msec after the onset of inspiration may be better measure of respiratory drive than mouth pressure in patients with intrinsic increase of airway resistance.