Astrocyte are the major glial cell type in the central nervous system (CNS), and analogous to macrophage, mediates the number of immune responses such as production of cytokines including tumor necrosis factor alpha (TNF-α) upon activation. TNF-α has been implicated in neuroimmunological disorders through killing oligodendrocytes and thus causing demyelination. It has been previously demonstrated that mitogen-activated T cells synthesized a 26 kDa precursor form of TNF-α which is bound to the surface of a membrane, and is later secreted as a 17 kDa mature version. In order to examine whether astrocytes would produce the transmembrane form of TNF-α, astrocytes were stimulated with biological stimuli and the membrane form of TNF-α was analyzed by Western blot and FACS analysis. When astrocytes are stimulated with lipopolysaccharide (LPS), IFN-γ/LPS, or IFN-γ/IL-1β, they were able to express a membrane-anchored TNF-α of approximately 26 kDa protein which was immunoreactive to an anti-TNF-α antibody, whereas unstimulated astrocytes or astrocytes treated with IFN-γ or IL-1β alone was not. Our FACS data were also consistent with the immunoblot analysis. Our result suggests that the membrane form of TNF-α expressed by activated astrocytes may cause local damage to oligodendrocytes by direct cell-cell contact and contribute to demyelination observed in multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE).