Molecular and Cellular Biochemistry, 49 143-149 (1982) Hydrogen Peroxide Mediated Killing of Bacteria D.P. Clifford and J.E. Repine Polymorphonuclear leukocytes (PMN) or neutrophils have multiple systems available for killing ingested bacteria. Nearly each of these incorporates H2O2 indicating the essential nature of this reactive oxygen intermediate for microbicidal activity. Following ingestion of bacteria by PMN, H2O2 is formed by the respiratory burst which consumes O2 and generates H2O2 from O2. H2O2 is deposited intracellularly near bacteria within phagocytic vacuoles where it can react with the MPO-H2O2-halide system to form toxic hyperchlorous acid (HOCl) and/or possibly singlet oxygen. H2O2 can also react with O2 and / or iron (Fe++) from lactoferrin or bacteria to form the highly toxic hydroxyl radical (OH). These mechanisms appear important since deficiencies of H2O2 production, myeloperoxidase or lactoferrin frequently increases their owner's susceptibility to infection. In particular, examination of PMN from infection prone patients with chronic granulomatous disease (CGD) most clearly demonstrates the importance of H2O2 in killing of bacteria. CGD PMN lack the capacity to effectively generate H2O2 and subsequently have impaired ability to kill catalase positive (H2O2 producing) bacteria. PMN also have catalase and glutathione peroxidase systems in their cytoplasms to protect themselves from the toxicity of H2O2. Finally, while H2O2 is critical for host defense, it can also be released extracellularly and thereby play a significant role in PMN mediated tissue injury.