A case of fulminant hemolytic anemia associated with a leptospiral infection is presented with morphologic and erythrocyte lipid studies. Both the frequency and pathogenesis of anemia in human leptospirosis is poorly understood. The anemia frequently observed in Weil's syndrome has been ascribed on clinical impression to blood loss, renal failure, and/or an ill-defined hemolytic process. However, hemolytic anemia associated with leptospirosis in animals is well documented and is due to hemolysins with phospholipase activity. Our patient's erythrocyte morphologic abnormalities on bright light and electron microscopy included particles of cells and cells with a thorny or spiculated surface suggesting that the hemolytic process was due to membrane injury. Measurement of the erythrocyte membrane lipids showed reductions in sphingomyelin and phosphatidylethanolamine suggesting that the observed hemolysis and morphologic changes resulted from phospholipases produced by the infecting leptospirae.