The frequency, type, and mechanism of the anemia caused by amphotericin B were studied in 30 patients with systemic fungal disease who received 37 courses of intravenous therapy. A decrease in hematocrit of 11 units or more was seen during 28 of the 37 courses. The anemia was normocytic, normochromic, and was not accompanied by reticulocytosis or erythroid hyperplasia. Red cell survival studies in five patients indicated that the rate of hemolysis was not affected by amphotericin administration. We concluded that the anemia was caused by suppression of red cell production by amphotericin imposed on mild preexisting hemolysis due to the systemic infection. The anemia was self-limited and return of the hematocrit to normal occurred in all but three cases after discontinuation of therapy.