We describe two female patients with systemic lupus erythematosus (SLE) who developed severe aplastic anemia. Although each patient had received multiple medications including diphenylhydantoin, the relationship to these drugs to the development of marrow aplasia was unclear. After administration of an oral androgen (oxymethalone) and corticosteroids, there was complete hematologic recovery. Both patients relapsed when oxymethalone was withdrawn, and both recovered when androgen therapy was reinstituted, with or without high-dose prednisone. In both patients, there was complete reversal of pancytopenia despite the presence of initially severe marrow aplasia (less than 10% cellularity). However, in both cases, prolonged androgen therapy (2 months) was required before hematologic improvement occurred. Androgens are known to stimulate hematopoiesis in man, and they appear to influence immune function in a mouse model of SLE. Thus androgens may be particularly useful in the treatment of SLE-associated aplastic anemia.