Edwin L. Thomas,* M. Margaret Jefferson, and Matthew B. Grisham abstract: Myeloperoxidase-catalyzed oxidation of chloride (Cl") to hypochlorous acid (HOC1) resulted in formation of mono-and dichloramine derivatives (RNHC1 and RNC12) of primary amines. The RNC12 derivatives could undergo a reaction that resulted in incorporation of the R moiety into proteins. The probable mechanism was attack of RNC12 or an intermediate formed in the decomposition of RNC12 on histidine, tyrosine, and cystine residues and on lysine residues at high pH. Incorporation of radioactivity from labeledamines into stable, high molecular weight derivatives of proteins was measured by acid or acetone precipitation and by gel chro-matography and electrophoresis. Whereas formationof RNC12 was favored at low pH, the subsequent incorporation reaction was favored at high pH. Up to several hours were required for the maximum amount of incorporation, which was less than 10% of the label in RNC12. For the amines tested, incorporation was in the order histamine> 1, 2-diaminoethane> putrescine> taurine> lysine> glucosamine> leucine> methylamine. Initiation of the reaction required HOC1, and oxidized forms of bromide, iodide, or thiocyanate did not substitute. Inhibitors of incorporation fell into three classes. First, ammonia or amines competed with the labeled amine for reaction with HOC1, so that largeramounts of HOC1 were required. Second, readily oxidized substances such as sulf-