Phagocytes respond to stimulation with a burst of oxygen consumption, and much, if not all, of the extra oxygen consumed in the respiratory burst is converted first to the superoxide anion and then to hydrogen peroxide (H2O2). Myeloperoxidase (MPO), which is released from cytoplasmic granules of neutrophils and monocytes by a degranulation process, reacts with the H2O2 formed by the respiratory burst to form a complex that can oxidize a large variety of substances. Among the latter is chloride, which is oxidized initially to hypochlorous acid, with the subsequent formation of chlorine and chloramines. These products of the MPO-H2O2-chloride system are powerful oxidants that can have profound biological effects. The primary function of neutrophils is the phagocytosis and destruction of microorganisms, and the release of MPO and H2O2 into the phagosome containing the ingested microorganism generally leads to a rapid microbicidal effect. Neutrophils from patients with chronic granulomatous disease (CGD) have a microbicidal defect that is associated with the absence of a respiratory burst and, thus, H2O2 production. Neutrophils from patients with a hereditary MPO deficiency, who lack MPO, also have a microbicidal defect, although it is not as severe as that seen in CGD. MPO and H2O2 also can be released to the outside of the cell where a reaction with chloride can induce damage to adjacent tissue and, thus, contribute to the pathogenesis of disease. It has been suggested that pulmonary injury, renal glomerular damage, and the initiation of atherosclerotic lesions may be caused by the MPO system.