Adoptive immunization of recipient mice preinfected with lymphocytic choriomeningitis virus (LCMV) is mediated exclusively by virus-specific thymus-derived lymphocytes, when assayed in a short-term transfer model. Protection, measured as reduction of LCMV plaque-forming units in spleens, is conferred only if donors of immune spleen cells and recipients share the K or the D region of the H-2 gene complex. I region compatibility is neither necessary nor sufficient. The F1 leads to Parent combination is as effective as a syngeneic system. Admixture of a 6-fold excess of immune allogeneic cells did not impair the protective effect exerted by syngeneic immune spleen cells in vivo. Furthermore, allogeneic spleen cells or target cells added in syngeneic systems in vitro did not allogeneicly inhibit or suppress cytolytic activity. H-2 mutant mice B6. H-2bf did not protect wild type H-2Kb B10.A(5r) or vice versa. Therefore, these mice define the gene(s) coding for the relevant cell-surface structure involved. These results are consistent with the idea that immune T cells, which are specific for virally altered cell-surface self structures impair virus growth in vivo either by lysing target cells, probably before infectious virus is released, or alternatively via activities exerted by lymphokines.