Experimental allergic encephalomyelitis (EAE), an animal model for multiple sclerosis (MS), is a paralytic disease of the central nervous system (CNS) mediated by T-lymphocytes reactive to myelin basic protein (MBP), Lewis rats actively immunized with fragment 68 to 82 of guinea pig MBP develop a monophasic disease with spontaneous recovery, Lymphocyte recognition of the primary encephalitogenic sequence of MBP (fragment 68 to 82) is V(beta)8.2 T cell receptor (TCR) skewed [1-3]. Lewis rats in clinical remission at 1 month and 3 months after spontaneous resolution of EAE retain V(beta)8.2 T-lymphocytes in the CNS when analyzed by reverse transcriptase polymerase chain reaction or in situ hybridization, In contrast, 1 and 3 months after clinical remission from syngeneic bone marrow transplantation, V(beta)8.2 T lymphocytes are absent from the CNS. During clinically active EAE and inflammatory breakdown of the blood-brain barrier, immune ablation and reconstitution with syngeneic bone marrow results in clinical tolerance of the new immune system to myelin. (C) 1995 Wiley-Liss, Inc.