Compared to single-agent therapy with hydroxyurea or myleran (155 patients), intensive chemotherapy with vincristine, cytosine arabinoside, prednisone and cyclophosphamide (60 patients) or anthracyclines (37 patients) showed significant survival improvement overall (p less than 0.01) and among intermediate- and high-risk patients. Of 51 patients treated with human leukocyte alpha interferon (IFN-alpha), 36 (71%) had complete hematologic remission (CHR); 20 patients (39%) showed Ph suppression which was persistent in 13 for greater than 21 months. Survival was better in patients obtaining remission with IFN-alpha. Recombinant gamma interferon (IFN-gamma) was also active in chronic myelogenous leukemia. Therapy with combined IFN-alpha + IFN-gamma has been initiated. Compared to the expected survival, the observed survival is favorable for IFN-alpha and the combined chemotherapy and IFN-alpha programs. Future therapeutic trials will incorporate initial IFN therapy followed by cyclic intensive chemotherapy at 6-month intervals and IFN maintenance between chemotherapy cycles.