Myeloperoxidase (MPO) is one of the essential components of the antimicrobial systems of polymorphonuclear neutrophils. It is unique in having a globin-like standard reduction potential of the ferric/ferrous couple. Here, it is shown that ferrous MPO heterolytically cleaves hydrogen peroxide forming water and oxyferryl MPO (compound II). The two-electron oxidation reaction follows second-order kinetics with the apparent bimolecular rate constant being (6.8 +/- 0.6) x 10(4) M-1 s(-1) at pH 7.0. After depletion of (micromolar) H2O2 compound II slowly decays to ferric MPO, whereas upon addition of millimolar H2O2 to ferrous MPO, compound III (oxyperoxidase) is formed in a sequence of two reactions involving compound II formation and its direct reaction with H2O2, which also follows second-order kinetics [(78 +/- 2) M-1 s(-1) at pH 7.0]. It is discussed how these reactions contribute to the interconversion of compound II and compound III and could explain the catalase activity of MPO. (C) 2003 Elsevier Inc. All rights reserved.