In order to elucidate the role of biological response modifiers (BRMs) in anti-tumor immunotherapy, we examined their effect on the induction of anti-tumor immunity in low-responder mice which hardly exhibit anti-tumor resistance against syngeneic Rous sarcoma virus (RSV)-induced tumors, such as B10 or B10.BR mice. The anti-tumor immunity induction in the low-responder mice was 0% on immunization with mitomycin C-treated syngeneic tumor cells alone. However, if BRMs were used as an adjuvant, BCG cell wall skeleton, OK-432 or lentinan augmented the induction of anti-tumor immunity to 50%, 33% and 33%, respectively. In the low-responder mice treated with BRMs, the anti-tumor immune cells had antigen-specificity at the induction phase of in vitro restimulation but not at the effector phase of target cell lysis by the stimulated cells. When T cells were depleted from immune spleen cells just before in vitro stimulation, cytotoxicity was not induced. Furthermore, cytotoxicity was not induced if accessory cells were removed from immune spleen cells at the induction phase. However, cytotoxicity at the effector phase was not mediated by T-lymphocytes, but by non-T cells. These results suggested that the induced cytotoxicity in low-responder mice was associated with the delayed-typed hypersensitivity-like effector mechanism.