This study examined the immunological responsiveness of the myelin deficient (md) rat, and its immune response to transplanted allogeneic glial cells, with and without immunosuppression therapy. Skin grafts from an ACI strain of rat were found to be acutely rejected by Wistar md rats. Anti-donor cytotoxic antibody was produced and alloreactive T helper cells were expanded in these mutants after skin sensitization. Equivalent high frequencies of precursor cytotoxic T lymphocytes (pCTLs) specific to the ACi MHC antigens were observed in both normal controls and mutants. An immune response was noted when allogeneic glial cells were transplanted into the spinal cords of md rats, which was effectively suppressed for 2 weeks post transplantation by treatment with either cyclosporin A (CsA) or a monoclonal antibody to the interleukin-2 receptor (IL-2R). These results demonstrate that md rats are immunocompetent, but that CNS allograft rejection can be prevented by immunosuppressive agents.