Theiler's virus causes, in the susceptible SJL/J mouse, a chronic demyelinating disease that resembles multiple sclerosis. Demyelination is at least in part immune mediated and coincides with the infiltration of the central nervous system by T lymphocytes. We analyzed the repertoire of the T cell receptor (TcR) beta-chain for each V beta-J beta combination, in spinal cord and spleen T cells of infected animals. All V beta families were detected in spinal cord as well as in spleen, as if the central nervous system were undiscriminantly invaded by T cells in the infected animals. Some T cells, defined by specific V beta-J beta combinations, were expanded in the spinal cord but not in the spleen, most probably because of an antigen-driven response. The TcR beta-chain repertoire of infiltrating T cells was the same at the onset of demyelination as when the disease was full-blown. These results provide the first description of the repertoire of the T cells which infiltrate the central nervous system during the course of this disease.