The cardiovascular, renal, pulmonary, and dermatologic toxicities of interleukin-2 (IL-2) and gamma-interferon (IFN) are well described. However, autoimmune toxicities have only recently been noticed. The authors report the development of warm autoantibodies against erythrocytes in a patient receiving IL-2 (3.75 x 10(6) cetus units/m2 intravenous bolus three times per week) and gamma-IFN (0.1 mg/m2 subcutaneously three times per week) for metastatic renal cell carcinoma. Other potential causes of autoantibody formation, such as drugs, infection, and collagen vascular disease, were excluded. Both gamma-IFN and IL-2 have the potential to trigger or exacerbate autoimmunity due to either aberrant expression of restricted antigens or inhibition of normal cellular immune suppressor mechanisms.