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1. Dogs injected intravenously with dog erythrocytes containing one or more antigenic factors lacking in their own red cells developed iso-hemagglutinins and hemolysins exhibiting characteristics of immune antibodies. 2. Transfusions of incompatible whole dog blood and plasma were carried out under controlled conditions. Pretransfusion observations were made and followed by closely spaced post-transfusion measurements of serologic and hematologic alterations. 3. The rate of destruction of incompatible donated corpuscles was determined by tagging the cells with radioactive iron and also by employing the technique of differential agglutination of erythrocytes. It was thereby shown that all of the incompatible donated cells disappeared from the recipient’s circulation within the first thirty to ninety minutes following transfusion. The probable mechanisms and relative importance of intra- and extravascular destruction of erythrocytes are briefly discussed. 4. Destruction of recipient dogs’ corpuscles by donated immune plasma was relatively slow, and spherocytosis and increased osmotic fragility of the recipients’ cells were evident for periods as long as twenty days. These observations are compared with those made in human beings after transfusions of plasma and of blood from dangerous universal donors. 5. The titer of complement in the sera of recipient dogs was sharply reduced for at least five hours after all transfusions of incompatible whole blood, but isoagglutinin titers were less regularly reduced after such transfusions. 6. Other notations of interest included estimates of the concentrations of serum bilirubin, sodium and potassium, determinations of clotting time, prothrombin concentration, and observations on red cell morphology, intravascular erythrophagocytosis, and shifts in distribution of leukocytes and in the electrophoretic patterns of plasma.

Each of 4 dogs was given two successive transfusions of incompatible dog erythrocytes at intervals of ninety or one hundred and twenty minutes. Measurements were made of the concentration of hemoglobin, complement and isoantibody in the plasma or serum of the recipients and of the rate of disappearance of the donated cells labeled with radioactive iron. In each experiment the donated red corpuscles were destroyed much more slowly after the second transfusion than after the first, and the hemoglobinemia produced by the first transfusion was not appreciably augmented by the second transfusion. The successive transfusions at short intervals were considered nearly equivalent to single large transfusions but permitted separate study of the effects produced. The rate of hemolysis was influenced by the initial titers of both antibody and complement. In dogs with high antibody titer, available complement appeared to limit the rate of destruction of incompatible donated cells. In the presence of adequate complement the rate of hemolysis was limited by the disappearance of antibody when the initial titer of antibody was low. Limitation of the degree of hemoglobinemia due to limitation of the rate of destruction of transfused incompatible erythrocytes and the rather efficient clearance of plasma hemoglobin explains in part the failure of some hemolytic transfusion reactions to produce severe or fatal renal damage. It is emphasized that most investigations of hemoglobinuric nephrosis in animals have dealt with the injection of hemoglobin solutions which resulted in hemoglobinemia of much greater intensity than it has been possible to produce by transfusion of large volumes of incompatible red corpuscles.

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