A series of experiments were performed on anesthetized dogs in which varying quantities of normal canine erythrocytes damaged by incubation with N-ethylmaleimide were injected into the circulation. Cell sequestration and catabolism of hemoglobin to carbon monoxide remained normal after injections that contained from 0.058 to 0.154 g of hemoglobin per kg of body weight. After administration of larger quantities of these cells, from 0.154 to 0.364 g of hemoglobin per kg of body weight, sequestration remained normal but the rate of catabolism of hemoglobin to carbon monoxide reached a maximum. Large quantities of hemoglobin entered the plasma in these experiments at a time when cell sequestration in the reticuloendothelial system appeared to be virtually complete. After injection of even larger quantities of damaged erythrocytes, 0.545 and 0.552 g of hemoglobin per kg, sequestration became slightly delayed, but was complete. These data appear to indicate that (a) the maximal rate of hemoglobin catabolism in normal anesthetized dogs averages approximately 0.07 g/kg of body weight per hr; (b) hemoglobinemia can result from "overloading" the reticuloendothelial system with damaged sequestered cells and, therefore, may not always indicate "intravascular" hemolysis; and (c) the sequestering function of the reticuloendothelial system appears not to limit the maximal rate of catabolism of hemoglobin. The limiting parameter or parameters were not defined in these studies.