Human neutrophils were found to generate an unusual class of oxidants with a half-life of approximately 18 hours and with characteristics similar to, if not identical with, those of N-chloroamines. These neutrophil-derived N-chloroamines have sufficient oxidizing potential to attack sulfhydryl- or thioether-containing compounds and can react with both a methionine-containing chemotactic peptide and a plasma protease inhibitor. As judged by their stability and selective reactivity, the N-chloroamines generated by stimulated neutrophils may play an important role in the local and systemic regulation of inflammatory events in vivo.