Immunization with attenuated activated autoreactive T cell lines and clones induces a response in syngeneic animals which can induce protection or recovery from autoimmune disease. This process has been termed T cell vaccination. The aim of the present study was to investigate the effect of immunization with MHC-reactive T cells on the mixed lymphocyte reaction (MLR). By injecting attenuated activated T cells primed for an alloantigen, we markedly reduced the MLR in both rats and mice. This depression appeared to be mediated by active suppression; lymphoid cells from T cell-vaccinated animals suppressed the MLR responsiveness of T cells from naive animals. Suppression of the MLR was not restricted to the major histocompatibility complex (MHC) alleles used to prime the animals from which the T cell vaccines were prepared; the MLR to other MHC allelic stimulator cells was also suppressed. This MHC-unrestricted suppression could not be attributed to an anti-ergotypic response to non-MHC-linked activation markers on T cells; an anti-ergotypic response augmented rather than suppressed the MLR. We herein propose that T cell vaccination might influence the MLR by suppressing the responses of diverse T cells which bear shared T cell receptor idiotypes.