Fas ligand (FasL) and Fas are mediators of apoptosis, which are implicated in the peripheral deletion of autoimmune cells, activation-induced T cell death, and cytotoxicity mediated by CD8(+) T cells. Fas is also believed to be involved in several central nervous system diseases, but until now, the effector cells expressing Fast in the brain have not been identified. We investigated the expression levels of Fas and Fast with the stimulation of cytokines and the possible effector cells targeting Fas-bearing cells. Our data demonstrated that: 1) Fast is expressed constitutively on astrocytes taken from a fetus or an adult and that its expression increases when these cells are treated with IL-1, IL-6, or TNF-alpha in which the pretreatment of IFN-gamma triggers astrocytes to express more Fast; 2) astrocytes induce apoptosis in MOLT4 cells through Fast; 3) Fas is also expressed constitutively and is upregulated by IL-1, IL-6, or TNP-alpha in which the pretreatment of IFN-gamma triggers astrocytes to express more Fas; 4) apoptosis occurs when fetal astrocytes are treated with agonistic: anti-Fas IgM Ab after culture with IFN-gamma and TNF-alpha; and 5) TNF-related apoptosis inducing ligand is up-regulated in fetal astrocytes with stimuli of IL-1 or TNF-alpha. These findings suggest a possible role of astrocytes in the induction of apoptosis in central nervous system diseases.