Pilot studies were conducted to evaluate the toxicity and efficacy of two relatively marrow-sparing chemotherapy regimens in the treatment of advanced or progressive epidemic Kaposi's sarcoma. Chemotherapy regimens consisted of bleomycin (10 mg/m2), vincristine (1.4 mg/m2, 2 mg maximum) and Adriamycin (doxorubicin) at either 10 mg/m2 (Group I) or 20 mg/m2 (Group 11). The therapy was given intravenously, every 2 weeks, until intolerable toxicity or maximum antitumor response. Thirty-three patients were treated. Although the patient populations were similar regarding pretreatment prognostic factors, the patients were not assigned randomly to these two treatment regimens. Major responses (complete or partial remission) were attained in 79% of the cases. The treatment-related toxicities consisted of mild to moderate nausea, hair loss, and peripheral sensory neuropathy. Bone marrow suppression consisted primarily of neutropenia (< 1000/mm3) which occurred in a third of the patients. Variables significantly associated with shorter survival included hemoglobin (< 10 g/dl), low Karnofsky performance status (< 70%), and weight loss. Opportunistic infections occurred in the majority of cases during administration of chemotherapy, and were most likely related to severe cell-mediated immune dysfunction and low CD4positive lymphocyte counts.