Adoptive transfer of CD8 T cells has the potential to cure infectious or malignant diseases that are refractory to conventional chemotherapy. A practically important but still unanswered question is whether mixtures of protective CD8 T cells with different epitope specificities mediate more efficient effector cell functions than do the monospecific individualCD8Tcell populations. In this study, we have addressed this issue for models of viral and bacterial infection. CD8 T cell-mediated cytotoxicity in vitro and protection in vivo were assessed to test whether CD8 T cell lines cooperate in target cell lysis and control of infection, respectively. Our data clearly show that mixtures of cytolytic T cell lines specific for different epitopes of either murine cytomegalovirus or Listeria monocytogenes do not act synergistically. An efficient anti-infectious protection thus proved to be dependent primarily on the number of transferred protectiveCD8Tcells rather than on the cooperative effects of multiple specificities.