The tolerance and toxicity of interferon-y (IFN-y) was assessed in a phase I/II study of 21 patients with acquired immune deficiency syndrome (AIDS). A highly purified preparation of human recombinant E. coli-produced IFN-y was given i.v. twice weekly for an 8 week period. Patients were enrolled in the study in groups of four or five; the initial group received an IFN-y dose of 0.03 mg/m2 and subsequent groups received higher IFN-7 doses of 0.3, 1, or 3 mg/m2. Toxicity resulting from IFN-7 was minimal and the therapy was well tolerated even at the maximum dose (3 mg/m2). No patients developed antibodies that neutralized IFN-y. Clinical responses were observed in 3 of 17 patients with Kaposi's sarcoma (KS). A complete clinical response was achieved in one individual and a partial, temporary regression of KS lesions was observed in two other patients. HIV p24 antigen was decreased in plasma samples obtained from six of nine patients with initially detectable HIV protein. These data suggest that IFN-y should be considered as a therapeutic agent, possibly with other antivirals, in the treatment of patients with AIDS.