Kaposi's sarcoma (KS) is common in individuals infected with the human immunodeficiency virus (HIV-1). Although KS is frequently indolent, it can also be aggressive and life-threatening, especially in patients with pulmonary involvement (PKS), who have poor survival rates when untreated. In an effort to develop treatment regimens for PKS that would prolong life or reduce clinical symptoms, we used combination chemotherapy to treat 18 patients who had AIDS and PKS; 13 (72%) of them had a history of previous opportunistic infections. Doxorubicin, bleomycin, vinblastine, vincristine, actinomycin D, and dacarbazine were used in 3-week cycles with concomitant zidovudine, zalcitabine (dideoxycytidine), or didanocine (dideoxyinosine). Antiviral therapy was continued with chemotherapy. A partial or complete response to chemotherapy was obtained in 15 of the 18 patients (83%), as characterized by clearing of infiltrates on chest films and resolution of dyspnea and cough. Only 2 patients had opportunistic infections during treatment. Median survival was 9 months; patients who received dose reductions in less than three cycles of chemotherapy survived more than 1 year. Most deaths were related to unresponsive PKS. These results indicate that patients with symptomatic PKS can be safely and effectively treated with combination chemotherapy while receiving myelosuppressive drugs such as zidovudine. Such patients receive substantial relief from dyspnea and cough. Survival for treated patients exceeds survival for untreated historical controls.