Abstract Results of investigations in twenty-four cases of acute hemolytic anemia are presented. Among the associated conditions which appeared to be causally related to the anemia were infections, ingestion of drugs and chemicals, malignant diseases, acute glomerulonephritis, thrombotic thrombocytopenic purpura, idiopathic autoimmune hemolytic anemia, paroxysmal nocturnal hemoglobinuria and trauma. In many cases there was no discernible underlying condition and the pathogenesis of the hemolysis could not be discovered. Initial symptoms frequently included chills, high fever, abdominal pain and vomiting. The spleen and liver were not markedly enlarged and jaundice was often lacking. In some patients the clinical picture resembled an acute infection or a surgical abdominal condition. Laboratory findings which aided in establishing the existence of acute hemolysis included spherocytosis, Heinz bodies, methemalbuminemia, hemoglobinuria and the absence of haptoglobins in the serum. The Coombs' test result was usually negative. Signs of hemolysis and of increased erythropoiesis, such as reticulocytosis and erythroid hyperplasia of the bone marrow, did not always appear concurrently. In the clinical management of these patients it was found important to prevent shock and acute tubular necrosis by transfusion and proper attention to fluid and electrolyte balance. Corticosteroids were seldom required. Regardless of the initial severity of the anemia, the prognosis for complete recovery was good in patients who had no serious underlying disease.