Hemoglobin and globin alone, supplemented, or modified in various ways are seriously considered as plasma substitutes. Human globin given to doubly depleted (anemic and hypoproteinemic) dogs by vein contributes to the production of new hemoglobin and plasma protein, but there is some toxicity and weight loss. Dog hemoglobin given intraperitoneally is better tolerated and somewhat more completely utilized with more blood proteins formed and less weight loss. Dog globin (tryptic digest) given by vein in anemic dogs is associated with a moderate production of new hemoglobin. Horse globin by mouth contributes to the formation of new hemoglobin in the standard anemic dog. Dog hemoglobin given intraperitoneally in protein fasting, non-anemic dogs is well utilized to maintain nitrogen and weight balance. A dl-isoleucine supplement fails to improve this utilization of hemoglobin for maintenance in the dog. A small supplement of dl-methionine greatly improves the utilization of dog hemoglobin for maintenance in the dog and further addition of isoleucine is without effect. The intermediary metabolism of dog hemoglobin is not yet worked out. Electrophoretic analyses (Table 6) suggest that globin appears in the peripheral circulation after intraperitoneal injections of hemoglobin.