Polymorphonuclear leukocytes (PMNs) release the contents of granules during their migration to inflammatory sites. On liberation from the first leukocyte to enter injured tissue, the granule proteins play a central role in the early inflammatory response. In particular, mononuclear phagocytes interact intimately with PMNs and their secretion products. PMN granule proteins enhance the adhesion of monocytes to the endothelium and stimulate subsequent extravasation of inflammatory monocytes. At the site of inflammation, PMN granule proteins activate macrophages to produce and release cytokines and to phagocytose IgG-opsonized bacteria. Furthermore, by direct cell–cell contacts, PMNs activate monocyte-derived dendritic cells, thereby enhancing antigen presentation. Efforts in this field might lead to the development of drugs for specific modulation of innate immune functions.