A macrophage-mediated antibody-dependent cellular cytotoxic reaction has been described in a syngeneic murine mammary adenocarcinoma model. The antibody appears to be present in two forms, one apparently complexed with antigen and the other identified as 7S immunoglobulin on Sephadex G-200 and as the IgG2a subclass by blocking of Fc receptors on the macrophages. This antibody is first detected in mice with regressing tumors. Tumor cells from immune mice appear to be coated with this antibody, as they are sensitive to the effects of normal macrophages in vitro, whereas tumor cells from immunologically compromised mice are not. Thus, a macrophage-dependent reaction probably is relevant in the in situ immune defenses against this tumor.