Kaposi's sarcoma (KS) was one of the first AIDS-defining illness identified, and continues to be a source of considerable morbidity and mortality. The most current information regarding the pathogenesis and biology indicate that a variety of cellular cytokines and products, including basic fibroblast growth factor (FGF) are involved in the growth of KS, particularly in stimulating angiogenesis and neovascularization. Pentosan polysulfate is a sulfated polysaccharide (MW 6000 Daltons) that has been used in Europe as an anticoagulant for many years. Recently, pentosan has been shown to block cell surface receptor binding of FGF and to possess activity against certain FGF-dependent tumor cell lines. We thus instituted a feasibility (pilot) study administering pentosan to patients with AIDS-KS. Sixteen patients were enrolled in the trial. While no patient had either a complete or partial response, 7 patients had stable disease which might indicate a stabilization resulting from an inhibition of growth factors. The dose-limiting toxicities identified were thrombocytopenia and anticoagulation. There were no significant alterations in CD4 cells in [HIV p24 antigen levels. We have developed a KS cell line and are now attempting to develop other therapeutic strategies.