Murine interleukin-4 (IL-4) exhibits potent antitumor activity when present at the site of tumor cell challenge. Associated with tumor cell death is the appearance of an inflammatory infiltrate comprised predominantly of eosinophils and macrophages, but with few lymphocytes. Antibodies that specifically block the accumulation of granulocytes at the site of inflammation were injected in vivo to define the cell type responsible for the antitumor action of IL-4. These studies implicate eosinophils in IL-4-mediated tumor cytotoxicity. The lymphoid-independent nature of IL-4 action is supported by the analysis of mutant mouse strains with defined lymphocyte immunodeficiencies. The observed regression of established tumor masses by localized IL-4 action provides a rationale for exploring IL-4-mediated tumor killing as a potential therapy for human malignant disorders.