It has been suggested that Fas ligand (FasL), expressed by several neoplastic cell lines and some tumors in vivo, is able to trigger the apoptotic process in activated T-lymphocytes and may constitute a key element of the immunological escape mechanisms used by many types of neoplasia. In order to evaluate the possible role of Fas-mediated apoptosis in Kaposi's sarcoma (KS), we have studied the immunocytochemical expression of Fas and FasL in biopsy specimens showing different histopathological stages of classic KS (C-KS) and AIDS-associated KS (AIDS-KS), as well as in cultured cells derived from C-KS lesions. KS biopsy tissue failed to show Fas expression in all epidemiologic forms and histopathologic stages studied, while FasL positivity was present in a small number of cells in just a few cases. Double immunostaining ruled out the lymphocytic nature of these cells, whose morphology in adjacent sections stained with hematoxylin and eosin was consistent with KS cells. In contrast, cultured KS cells exhibited strong immunocytochemical cytoplasmic expression of both Fas and FasL. These findings indicate that the Fas-FasL system does not play a major role as a trigger of apoptosis in KS cells in vivo and that the upregulation of these molecules observed in KS cells in vitro probably is the result of cell stress induced by growth in culture.