The cell surface receptor Fas (FasR, Apo-1, CD95) and its ligand (FasL) are mediators of apoptosis which have been shown to be implicated in peripheral deletion of autoimmune cells, activation-induced T cell death, and one of the two major cytolytic pathways mediated by CD8+ cytolytic T cells. Analysis of FasL expression during mouse embryogenesis and in adult tissues reveals that FasL, although initially thought to be restricted to lymphoid cells, is constitutively expressed in a wide array of non lymphoid tissues. FasL mRNA is detectable in mouse embryos from 16.5-d onwards in epithelial cells of the submaxillary gland, and neurons of the developing nervous system. In general, FasL mRNA was not detectable in characteristic sites of embryonic programmed cell death. In the adult mouse, by RNase protection analysis, FasL mRNA is detectable in all 20 tissues tested except for the heart and pancreas. Similar analysis performed simultaneously for Fas indicates that several tissues, including the thymus, lung, spleen, small intestine, liver, seminal vesicle, prostate and uterus co-express the two genes. Most tissues constitutively co-expressing Fas and FasL in the adult mouse are characterized by apoptotic cell turnover, and many of those expressing FasL are known to be immune-privileged. The pattern of FasL expression in mice suggests that FasL may be implicated in the regulation of physiological cell turnover, and the protection of tissues against potential lymphocyte mediated damage.