Pulmonary ventilation was measured during breathing of 100%, 20%, and 10% oxygen in lightly anesthetized dogs. The animals were divided into three groups; dogs in each group were studied at their normal hematocrit and after complete recovery from exchange transfusions with either plasma, packed red cells, or normal blood. Exchange transfusions with normal blood or elevating the hematocrit to a mean of 54% did not alter minute ventilation at any of the inspired oxygen concentrations tested. When dogs were made anemic (mean hematocrit 11%), they consistently ventilated more at all inspired oxygen concentrations, and they had a faster and approximately 40% greater ventilatory response to hypoxia than before they were made anemic. At a given inspired oxygen concentration [Formula: see text] was the same, but [Formula: see text] was consistently lower in anemic than in non-anemic animals. Ventilation increased as [Formula: see text] fell, and this relation was independent of existing hematocrits. A hypothesis has been proposed that pulmonary ventilation may, in part, be regulated by average tissue [Formula: see text] and systemic vascular resistance, with baroreceptors acting as the mediators of the response. We also observed that hemoglobin levels and hematocrits rose significantly during acute hypoxia in non-splenectomized dogs, causing an increase in the oxygen-carrying capacity of approximately 25% in anemic, of 6% in normal, and of 3% in polycythemic dogs.