A crucial question in the study of immunological reactions in the central nervous system (CNS) concerns the identity of the parenchymal cells that function as the antigen-presenting cells in that organ. Rat bone marrow chimeras and encephalitogenic, major histocompatability--restricted T-helper lymphocytes were used to show that a subset of endogenous CNS cells, commonly termed "perivascular microglial cells," is bone marrow-derived. In addition, these perivascular cells are fully competent to present antigen to lymphocytes in an appropriately restricted manner. These findings are important for bone marrow transplantation and for neuroimmunological diseases such as multiple sclerosis.