Apoptosis mediated by members of the tumor necrosis factor (TNF)–nerve growth factor superfamily plays a crucial role in the interaction of the nervous and the immune system. On the one hand, it is involved in the defense mechanisms of the brain, the immune privilege. On the other hand, it is involved in the induction of glial–neuronal cell death in neuroinflammatory diseases. Here, we show that in contrast to the other known death ligands, TNF-related apoptosis-inducing ligand (TRAIL) is not constitutively expressed in the human brain, whereas both apoptosis-mediating and apoptosis-blocking TRAIL receptors are found on neurons, astrocytes, and oligodendrocytes. Thus, the brain differs from other immune-privileged organs, such as the placenta, with the TRAIL receptor–TRAIL system not being part of the immune privilege of the brain. Conversely, this death receptor–ligand system might well play an important role in T cell-mediated autoimmune diseases of the CNS such as multiple sclerosis.