OBJECTIVE Kaposi's sarcoma occurs commonly in patients with the acquired immunodeficiency syndrome (AIDS). Kaposi's sarcoma may remain localized or disseminate to involve visceral organs such as the lungs. Disseminated pulmonary involvement, when it occurs, is often fatal. Effective therapy may improve survival in such patients. We herein report on 20 patients with disseminated pulmonary Kaposi's sarcoma treated with cytotoxic chemotherapy. METHODS Twenty previously untreated patients with pulmonary Kaposi's sarcoma were identified. All were treated with cytotoxic chemotherapy consisting of either Adriamycin alone, a combination of Adriamycin, bleomycin, and vincristine (ABV), or bleomycin and vincristine (BV). The response to therapy and factors affecting prognosis were analyzed retrospectively. RESULTS Twelve (60%) patients showed a favorable response to therapy. The median survival from the initiation of chemotherapy for the 12 responders was 10 months (range: three to 31 + months) versus six months (range: one to 17+ months) for the non-responders. Eleven of the patients showing a response received ABV or BV combination chemotherapy (p = 0.004). Survival was shortened by the presence of either pleural effusion (p = 0.002), T4 lymphopenia of less than 100/mm3 (p = 0.03), or both at study entry. CONCLUSIONS In patients with pulmonary Kaposi's sarcoma, combination chemotherapy consisting of ABV or BV is associated with dramatic clinical and functional improvement. The median survival of 10 months demonstrates the value of combination chemotherapy in this group of patients.