The specificity and efficiency of tumor-cell lysis by the retargeting of murine cytolytic lymphocytes (CTL) with bispecific antibodies was examined. Bispecific antibodies (also known as heteroaggregated or hybrid antibodies) were produced by the chemical coupling of monoclonal antibodies (MAbs) against H-2 antigens and the murine T-cell receptor (TCR). Murine tumor cell lines which expressed on their plasma membrane an antigen reactive with one component of the bispecific antibody were efficiently lysed in the presence of polyclonal murine CTL. CTL capable of lysis were generated by stimulating spleen or lymph-node cells with ConA and IL-2, while unstimulated cells or cells incubated only with IL-2 showed no lysis of target cells with bispecific antibodies. Furthermore, the lysis of target cells by bispecific antibodies and CTL did not cause the lysis of bystander cells (cells not expressing an antigen recognized by the antibody which are mixed with the target cells). The efficient CTL-mediated lysis observed with these antibodies makes this a promising approach for the immunotherapy of human cancer.