Inoculation of mice with live influenza virus results in the induction of cytotoxic thymus-derived (T) lymphocytes and of bone marrow-derived (B) cells producing antiviral antibodies. An assay system was developed to evaluate both types of immune responses on a cellular basis within the same lymphocyte pool with no need to separate out the different effector cell classes. The test system represented a modification of the 51Cr-release assay. T-cell activity was measured exclusively in the absence of active complement using targets that were compatible for determinants encoded by the mouse major histocompatibility gene complex, H-2. H-2-different and even xenogeneic target cells were lysed in the presence of either non-inactivated fetal calf serum or normal rabbit serum as a complement source. Cytotoxicity was mediated in the latter case by direct interaction of B-cell-produced immunoglobulin directed to viral antigens expressed by the target cell and complement. Antibody-dependent cell-mediated cytotoxicity mechanisms did not contribute to cytotoxicity in the test system described. It was demontrated that the cytolytic B-cell responses of one particular strain of mice (BALB/c) against different influenza A viruses were restricted to the immunizing virus on the effector cell level. In another strain of mice (C3H), B cells revealed a broad cross-reactive response resembling that of killer T cells.