In this review the authors discuss three immunologically unique aspects of the central nervous system (CNS). The first relates to whether the CNS is really an immunologically privileged site. Although still somewhat controversial, the answer to that question is that the CNS is, to a large extent, an immunologically privileged site. The second unique aspect of the CNS is the origin and significance of the microglial cell. Some microglial cells seem to originate from the systemic circulation, whereas other microglial cells seem to have a primary CNS origin. The function of the microglial cell is that of a macrophage. In addition it may play an important role in the immune response of the CNS. Present evidence suggests that the microglial cell can be classified as a lymphoreticular cell and as such is the only member of this cell type present in the CNS under normal circumstances. The final unique aspect of the central nervous system is the cerebrospinal fluid (CSF). Under normal circumstances this fluid is essentially acellular, and the only immunoglobulins present are those that are passively derived by diffusion from the systemic circulation. However, in pathological situations (i.e., demyelinating diseases, infections, and possibly even tumors) a local immune response occurs within the CNS and can result in the production of immunoglobulins. At present the detection of such local immune responses in CSF is predominately of diagnostic value only. However, these local CNS immune responses almost certainly play an important role in the pathogenesis of the diseases in which they occur.