Even though the immune privileged status of the central nervous system (CNS) limits access of systemic immune cells through the blood brain barrier (BBB), an immune response can occur in this compartment with or without major breach of the BBB. In this review, we consider properties of resident cells of the CNS, that participate in regulating the neural antigen (Ag)‐directed immune responses implicated in autoimmune diseases such as multiple sclerosis (MS). Under such conditions, the CNS is usually viewed as the target or victim of the immune assault, because such immune responses are thought to be initiated and regulated within the systemic immune compartment. The CNS‐endogenous cells may themselves, however, initiate, regulate and sustain an immune response. We consider the immune regulatory functions within the CNS in terms of events occurring within the CNS parenchyma (microglia, astroglia) and at the vascular interface. These regulatory functions involve antigen presentation to T cells and polarization of the cytokine response of these cells. Such responses may contribute not only to the overall tissue injury in primary immune disorders but also in a wide range of traumatic, ischemic and degenerative processes. GLIA 29:293–304, 2000. © 2000 Wiley‐Liss, Inc.