Twenty-three patients with biopsy-proven Kaposi’s sarcoma and HIV infection were treated with recombinant interferon-alpha-2 a (Rofe-ron-A). Two dosage regimens were used: 21 patients received 18 × 106 units intramuscularly per day for 3 months, followed by injections of 18 × 106 units three times a week. The remaining 2 patients were treated with 2×18×106 units i.m. per day for 3 months. Three patients either refused further treatment or were lost to follow-up within the first few weeks. Thus, a median observation period of 7.5 months (range 1.5–17) was available for 20 patients. Within the first 3 months, 6 patients (30%) responded to treatment, 6 patients (30%) showed no progression, whereas in 8 cases (40%) progressive disease was noted. A similar rate of responders versus nonresponders was found after 6 months of observation. In progressive disease, interferon could be effectively combined with cytostatic drugs. Dose-dependent neurological and hematological side effects were observed in a few patients only. Opportunistic infections were diagnosed in 12 patients with a median onset of 6 months (range 1–10) after start of interferon treatment. The total number of lymphocytes expressing the CD4 antigen or the ratio of CD4 to CD8 positive cells were of prognostic value. These data suggest that interferon alpha is an active agent in the treatment of Kaposi’s sarcoma, that it shows tolerable side effects and can be combined effectively with cytostatic drugs in case of progression.