The aim of this study was to examine the outcome, adverse events and clinical complications of long-term chemotherapy with pegylated liposomal doxorubicin (PegLiposomal DOX) for human immunodeficiency virus (HIV)-associated Kaposi's sarcoma (KS) in the pre-highly active antiretroviral therapy (HAART) era. A phase II study over a 4-year period in a tertiary care university hospital was carried out. 52 acquired immunodeficiency syndrome (AIDS)-patients with advanced KS received long-term chemotherapy (71+/-51 weeks) with a mean of 22.8+/-18.2 cycles and a mean cumulative liposomal doxorubicin dose of 456+/-364 mg/m(2) (120-1040 mg/m(2)). Tumour burden, duration and dosage of PegLiposomal DOX, adverse events, opportunistic infections, immunological parameters and HIV load were measured. A complete (10%) or partial response (56%) was achieved while on chemotherapy. 10 patients (19%) showed stable disease. Tumour progression was observed in 8 patients (15%). Importantly, chemotherapy with PegLiposomal DOX was also successful after previous cytostatic therapy with bleomycin and vincristine. The most common adverse events included leucopenia, neutropenia, anaemia, and increased liver function tests. 34 patients (65%) developed new opportunistic infections and 29 patients (56%) died during the study period. To conclude, pegylated liposomal doxorubicin is a safe and effective drug for long-term chemotherapy of advanced (AIDS) KS without adverse effects on CD4 cell counts and HIV viral load.