The pathological destruction of collagen plays a key role in the development of inflammatory disease states affecting every organ system in the human body. Neutrophils localized at inflammatory sites can potentially degrade collagen by releasing a metalloenzyme, collagenase, which is stored in a latent inactive form. Triggered human neutrophils were shown to release and simultaneously activate their latent collagenase. The activation of the latent enzyme was coupled to an oxidative process that required the generation of a highly reactive oxygen metabolite, hypochlorous acid. Oxidative regulation of latent collagenase activity may be important in the pathogenesis of connective tissue damage in vivo.