Spleen cells from mice immunized with an allogeneic tumor when cultured with the specific tumor cells release into the supernatant a specific macrophage-arming factor(s) (SMAF) which binds nonspecifically to macrophages from both mice and rats and renders these cytotoxic to the specific tumor cells. SMAF also binds in an immunologically specific way to the target cells. SMAF-treated target cells grow normally in the absence of macrophages but are killed in the presence of normal macrophages. Thymus-derived cells are necessary for the production of SMAF since (a) after treatment with anti-theta serum immune spleen cells fail to release SMAF; (b) spleen cells from immunized T cell-deprived mice (thymectomized as adults followed by whole body irradiation and restored with bone marrow) fail to produce SMAF on stimulation with the specific target cells. While SMAF has the properties of a cytophilic antibody, it does not belong to one of the established classes of immunoglobulin since high activity is found after column separation in a fraction having a molecular weight between 50,000-60,000 daltons.