In vitro culture of murine spleen cells with Corynebacterium parvum (C. parvum) was found to induce lymphokine-activated killer (LAK)-like cells capable of killing both natural killer (NK)-sensitive and NK-resistant tumor cells as well as syngeneic macrophages (M phi). The induction of LAK-like activity by C. parvum was significantly inhibited by anti-interleukin-2 (IL-2) or anti-interferon (IFN) alpha, beta antibody (Ab), and it was further inhibited by the combination of two Abs, suggesting that the generation of killer cells by C. parvum was dependent on IL-2 and IFN(s) produced in the culture. It was considered that M phi were important in the induction of LAK-like cells by C. parvum because the depletion of M phi from spleen cells before culture with C. parvum significantly reduced the induction of killer activity. The majority of effectors mediating both tumor cells and M phi were Thyl+ and asialo-GM1 (aGM1)+, and the lysis of M phi by C. parvum-induced killer cells could be inhibited by the addition of cold YAC-1 tumor cells and P815 tumor cells, suggesting that the same population of effectors recognized tumor cells and M phi. These results demonstrated a possibility that the killing of M phi by C. parvum-induced killer cells might down-regulate anti-tumor effects of C. parvum.