The microbicidal action of leukocytes is thought to proceed in part through oxygen-dependent reactions. Molecular oxygen can be reduced to superoxide radical anion (O2-)1 which, along with its products, may react directly with the micro-organism, or H2O2 and halide may act as substrates for the halogenation of bacteria by myeloperoxidase. Both superoxide and myeloperoxidase-dependent reactions exhibit chemiluminescence in vitro and they appear to be major sources of light emitted from living cells that are in the process of phagocytizing foreign material. Most previous studies of chemiluminescence in leukocytes have employed particulates (zymosan, heat-killed bacteria, and polystyrene butadiene particles), which stimulate phagocytosis as well as O2 metabolism and in some cases appear to act as substrates in light producing reactions. Interest in the purely oxidative reactions as well as preliminary studies by Allred and Hill led us to the discovery that N-formylmethionyl peptides stimulate chemiluminescence. These unique compounds, which are found in procaryotes, were recently shown to stimulate both chemotaxis and lysosomal enzyme release in leukocytes. In this paper the authors describe some of the properties of N-formylmethionyl (F-Met) peptide-induced chemiluminescence in human polymorphonuclear leukocytes (PMN) and in PMN and macrophages from guinea pigs and rabbits.