Cardiovascular responses have been studied in baboons, after total exchange transfusion with hemoglobin solutions having various P50 values. At the end of the exchange transfusion, the hematocrit was 1.5%, the mean hemoglobin concentration was 4.4 g/dl, and the P50 varied between 12 and 26 mm Hg. Cardiac output did not change during the study, although heart rate increased, and stroke volume and MAP decreased. Hemoglobin concentration, per se, does not appear to be the critical stimulus for an increase in cardiac output with hemoglobin solution. In addition, the position of the hemoglobin-oxygen dissociation curve does not appear to influence these hemodynamic responses. The physiological response to anemia in the presence of hemoglobin solution appears different from that observed in the absence of plasma O2 carriers.