BACKGROUND Kaposi's sarcoma (KS), either in its endemic (African) form or its AIDS-related variant, is a common neoplastic disorder seen in Southern Africa. Chemotherapy has been proven to be very effective in advanced or relapsed African Kaposi's sarcoma, but much less so in AIDS-related, endemic KS. METHODS The study consists of a retrospective analysis of the results of chemotherapy alone in 17 patients with African KS (AKS) and in 32 patients with epidemic AIDS-related KS (EKS), treated at the Johannesburg General Hospital between 1982 and 1992. Single agents included vinblastine, actinomycin D, bleomycin, and vincristine; combined regimens were largely doxorubicin/vincristine/bleomycin or etoposide/methotrexate. Outcome classifications were: complete remission (CR), partial remission (PR), and treatment failure (TF). RESULTS Four of the 17 patients with AKS had CR, 10 a PR, and three were TF and died rapidly from their disease. The combined chemotherapeutic regimens produced marked symptomatic relief and even long-term remission in AKS. In patients with EKS, the response rate to chemotherapy was very low and of brief duration. No patient had a CR and debilitating side effects were common. CONCLUSIONS The African type of AKS is a chemo-sensitive tumor, whereas the endemic type EKS, like its Western counterpart, has a dismal prognosis.