Oxidative damage to biomolecules has been implicated in tissue damage during acute and chronic inflammation. One potential mechanism involves reactive oxygen species produced by peroxidases of professional phagocytes - neutrophils, monocytes, macrophages, and eosinophils. We have shown that activated phagocytes employ myeloperoxidase and eosinophil peroxidase to halogenate proteins, lipids, and nucleobases in vitro. The reaction pathways involve hypohalous acids, molecular halides, and interhalogen compounds. We have used sensitive and specific mass spectrometric methods to demonstrate that certain of these halogenated products are present in human inflammatory tissue. These observations indicate that myeloperoxidase and eosinophil peroxidase promote biohalogenation reactions in vitro and in vivo. We therefore propose that reactive species produced by peroxidases halogenate amino acids, proteins, nucleotide precursors, RNA, and DNA. Collectively, our observations indicate a novel mechanism for tissue damage by activated phagocytic white blood cells during inflammation. This process might alter proteins and genes, enabling phagocyte peroxidases to produce cytotoxic or even tumorigenic changes in inflamed tissue.