Hemolytic anemia with hemoglobinuria is frequently a striking clinical event indicative of extensive intravascular hemolysis. The condition lends itself to detailed study because of the morphologic abnormalities in the blood and bone marrow, the marked accumulation of hemoglobin and its derivatives in the blood plasma and urine, the aberrations of renal function incident to the hemolytic process and the variety of pathogenetic mechanisms which may give rise to it. During the past ten years we have had an opportunity to study carefully a large number of cases of hemoglobinuria; these are reported in this communication. Our cases do not include all the described varieties of hemoglobinuria, but direct attention to the types that occur in general civilian medical practice in temperate climates. They fall into four groups, namely, those presenting the Marchiafava-Micheli syndrome (paroxysmal nocturnal hemoglobinuria), those caused by drugs or cold hemagglutinins and an idiopathic variety. No attempt will be made in this paper to deal with the hemoglobinurias that we did not observe personally, such as hemoglobinuria of blackwater fever, favism, burns, bartonella infections, sepsis, snake bites, spider bites, syphilitic paroxysmal cold hemoglobinuria, myoglobinuria, march hemoglobinuria, hemoglobinuria following the intravenous infusion of distilled water or transfusions of incompatible blood or plasma and hemoglobinuria associated with the action of certain chemical agents. At the outset it is necessary to distinguish clinically between the hemoglobinurias and the larger group of hemolytic anemia without hemoglobinuria. In both, excessive destruction of red blood cells occurs, morphologic findings in the blood and bone marrow are similar and increased excretion of urobilinogen is the rule. The rationale for differentiation rests upon the probability of fundamental difference in the mechanisms of the hemolysis and, as discussed subsequently, the inapplicability of splenectomy in the treatment of hemoglobinuria. In some of the hemolytic anemias without hemoglobinuria the spleen occupies a cardinal position in the hemolysis. This is proved by the cessation of excessive hemolysis following splenectomy. In the hemoglobinurias, on the other hand, hemolysis is either initiated differently or proceeds in another location (e.g., the circulating blood), and the dominance of the spleen is not apparent. The hemoglobinuric states in which this concept is proved are: 1. Paroxysmal nocturnal hemoglobinuria in which splenectomy does not stop the hemolytic process. 2. Paroxysmal cold hemoglobinuria due either to cold hemagglutinins or to syphilis; hemoglobinemia can be shown to be a local process occurring in the blood of the chilled part. 3. Incompatible blood transfusions.