Spleen cells from mice exposed to 500 rad sublethal whole-body irradiation before immunization with 100 x 10(6) allogeneic spleen cells exhibited an enhanced cytolytic T-lymphocyte (CTL) activity. In contrast, this treatment completely abrogated the humoral alloantibody response, as measured by complement-mediated lysis. In addition to the observed dissociation between primary humoral and cell-mediated responses, the character of the in vitro secondary CTL response of spleen cells obtained from mice sublethally irradiated before alloimmunization was also modified. Although these spleen cells were perfectly capable of mounting a secondary response upon restimulation in vitro with intact allogeneic spleen cells, they were no longer capable of responding to subcellular alloantigen preparations. These results suggest that the cellular requirements for the induction of secondary CTL responses in vitro depend upon the nature of the antigen used for restimulation.