OBJECTIVE A phase II study was performed of single-agent liposomally entrapped doxorubicin ([LED] Doxil; Liposome Technology Inc, Menlo Park, CA) against locally advanced cutaneous/systemic AIDS-related Kaposi's sarcoma (KS). METHODS Thirty-four patients with AIDS-related advanced cutaneous/systemic KS were treated with 20 mg/m2 of LED every 3 weeks on an outpatient basis. The median age was 39 years and the median Karnofsky score was 70. All patients had poor prognostic disease as judged by AIDS Clinical Trials Group (ACTG) criteria. Nineteen of 34 patients had received prior chemotherapy for KS, although no patient had received prior anthracyclines. RESULTS An overall response rate of 73.5% (25 of 34) was observed. Partial responses (PRs) occurred in 67.7% (23 of 34) and complete responses (CRs) in 5.8% (two of 34). In patients who had received previous chemotherapy, the response rate was 68.4% (13 of 19), and all responses were PRs. The median time to response was 6 weeks. The median duration of response was 9 weeks. Toxicity according to World Health Organization (WHO) criteria was as follows: neutropenia (grade > or = 3), 34%; alopecia (grade 1 only), 9%; and nausea and vomiting (grade 1), 18%. One patient died of heart failure, which was not considered to be anthracycline-induced. CONCLUSIONS LED appears to be highly active against AIDS-related KS. The major toxicity is neutropenia, which seems to be progressive in patients who receive several cycles of therapy. Comparative studies of LED versus conventional chemotherapy are needed.