Patients with Philadelphia chromosome-positive chronic myelogenous leukemia (CML) were treated with a combination of alpha-interferon and gamma-interferon. Recombinant alpha-2a-interferon (Roferon-A, Hoffmann-LaRoche, Inc., Nutley, NJ) and recombinant gamma-interferon (Genentech, Inc., South San Francisco, CA) were administered on alternating weeks each at doses ranging from 2 to 10 MU/m2 given intramuscularly. Of the 27 patients, 11 (41%) achieved complete hematologic remission (CHR) and 3 (11%) achieved partial hematologic remission (PHR). Responses were seen among 9 of 22 (41%) patients treated during the chronic phase of the disease and in 2 of 5 (40%) patients treated during the accelerated phase/second chronic phase. Cytogenetic responses were seen in six patients, including one complete response and five minor responses. Toxicities included flu-like symptoms, which appeared to be more severe with gamma-interferon than with alpha-interferon, hypertriglyceridemia, and thrombocytopenia. In this limited study, an improved outcome was not observed for the combination regimen compared with alpha-interferon alone.