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 individual CD8 T cell 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 protective CD8 T cells rather than on the cooperative effects of multiple specificities.