Carbobenzoxy-phenylalanyl-methionine (CBZ-Phe-Met) is an inhibitor (antagonist) of the binding to the receptor on polymorphonuclear neutrophils (PMN) for a series of synthetic chemotactic oligopeptides. This inhibitor was studied for its effects on the following chemotactic factor-induced PMN functions: a) chemotaxis, b) granule enzyme release, c) cellular aggregation, and d) in vivo induction of neutropenia. Each of these functions when induced by the chemotactic tripeptides (formyl-methionyl-leucyl-phenylalanine or formyl-methionyl-methionyl-methionine) was inhibited by the antagonist. For each in vitro assay the concentration of antagonist causing a 50% inhibition of response was approximately 10-4 M and the dissociation constant for the antagonist was approximately 10-5 M. Inhibition was dose related, reversible, and competitive. In contrast to these results, the antagonist, CBZ-Phe-Met, did not inhibit any of the four PMN responses induced by the chemotactic fragment of C5. These results further strengthen the relationship between all four chemotactic factor-induced PMN responses and suggest that these chemotactic tripeptides induce each response by interacting with a single receptor. Antagonists of chemotactic factors may represent a new approach to the in vivo suppression of leukotactic factor-mediated biologic responses.