We have devised a sensitive means to assess the anti-tumor effect of cytokines that act via the mobilization of host-mediated defenses. This assay involves transfecting malignant cells to produce a specific cytokine (in this case, IL-4) and measuring the ability of transfectants to form tumors alone and when mixed with a variety of nontransfected tumor cells. In this way, we have identified a potent, non-cell autonomous, anti-tumor effect of IL-4 which is effective against a wide range of tumor cell types in vivo. The effect is reversed by anti-IL-4 antibody, correlates closely with levels of IL-4 production, and is evident in nu/nu mice. The anti-tumor effect seems to be mediated by an inflammatory infiltrate composed of eosinophils and macrophages.