Macrophages from mice treated with a novel antineoplastic agent, bisantrene, were shown previously to be highly active in inhibiting the proliferation of tumor cells in culture. These activated cells have now been found to protect mice from dying of progressive tumors when injected into animals. The effect was observed not only in a Winn-type tumor cell neutralization assay but also in a setting of therapeutic intervention. Multiple treatments with bisantrene-activated cells seemed more effective than a single treatment. Macrophages appeared to be the major effectors in this system, since treatment with carrageenan abolished the protective effect. Thus, present findings suggest that in addition to a direct cytotoxic effect of bisantrene, the activation of macrophages may contribute to the overall antitumor activity of the drug.