Measurements were made of O2 uptake, CO2 output and CO2 tension of arterial and mixed venous blood and expired alveolar gas in 28 anesthetized and paralyzed dogs ventilated with air at a constant rate. Retention of CO2 was not observed in the lateral decubitus position with either closed or open thorax. Induction of open pneumothorax resulted in an unexplained metabolic alteration characterized by an increase in O2 uptake and CO2 elimination and a decrease in plasma buffer base. Small amounts of CO2 were eliminated from exposed pleura. The left pulmonary artery was occluded (after left thoracotomy) and 1 hour later the left bronchus also was occluded—or the order was reversed. CO2 retention of major degree was observed after initial occlusion of the artery and retention of minor degree after occlusion of the bronchus. During the 2nd hour (after additional occlusion) the previously retained CO2 was eliminated. The results suggest that the ventilatory requirements are not influenced specifically by effects of lateral position, open pneumothorax, or small right-to-left shunts, but rather are determined to a large degree by the metabolic production of CO2 and the degree to which ventilation is distributed to perfused alveoli. Submitted on December 3, 1958