Despite the mechanical blood-brain barrier, activated T-cells can cross brain vessels. Thus, the CNS is routinely surveyed by immune competent cells; yet the healthy brain is not a target of antigen-specific immune reactions. Therefore, mechanisms must exist to prevent brain-antigen-specific T-cells from inducing immune responses. Data indicate that activated T-cells entering the CNS may undergo apoptosis rather than leaving the brain to induce immune responses. Applying RT-PCR, Western-blots, and immunocytochemistry, we have demonstrated expression of the apoptosis-inducing protein Fas ligand on astrocytes and neurons of apparently normal rat and human brains. FasL-positive astrocytes were often situated in close vicinity to cerebral blood vessels in vivo and induced apoptosis of Fas expressing Jurkat cells in vitro. We propose that similar to other immune privileged organs FasL-induced apoptosis of activated T-cells in the brain protects the tissue from self damaging immune attacks by forming an immunological brain barrier.