Treatment of AIDS-related Kaposi's sarcoma with cytotoxic chemotherapy is limited by toxicities of the various agents. Liposomal doxorubicin is a new treatment option for patients with Kaposi's sarcoma with potentially reduced toxicity. Three AIDS patients with different stages of tumor risk were enrolled in a study evaluating the safety and efficacy of liposomal doxorubicin at a dose of 10-20 mg/m2 every 2-4 weeks. Maximal duration of treatment was 86 weeks with a cumulative dose of 560 mg/m2. Criteria proposed by the AIDS Clinical Trials Group were used to define tumor stages and response to therapy. All patients showed partial responses after 40-100 mg/m2 total dose with reduction of tumor-associated edema and flattening of more than 50% of previously nodular or plaque-like lesions. One patient showed progressive disease after discontinuation of treatment for 8 weeks; Kaposi's sarcoma responded again partially on retreatment. Progression was also seen in one patient after dose reduction due to granulocytopenia and again during treatment of active cytomegalovirus retinitis. Serial measurements of cutaneous target lesion surface area did not indicate response. Increases in surface area, however, correlated with progressive disease. Toxicities included moderate leukopenia, aphthous stomatitis, and transient alopecia. Liposomal doxorubicin may well be valuable for long-term treatment of AIDS-associated Kaposi's sarcoma, especially in patients with extensive disease. However, controlled comparison with conventional treatment regimens is mandatory.