Neutrophils contain a collagenase that is stored in a latent form within the specific granule. With cellular activation, the latent enzyme is activated in association with the production of a variety of oxidants, including hypochlorous acid. We evaluated 4 nonsteroidal antiinflammatory drugs (NSAIDs) currently on the market and the new antiinflammatory/antirheumatic drug tenidap for their effects on the release of activated collagenase. In contrast to the 4 NSAIDs, tenidap profoundly inhibited the release of activated collagenase. This inhibition was predominantly due to interference with activation of the latent enzyme, rather than interference with enzyme release. The inhibition of collagenase activation was associated with a profound reduction in myeloperoxidase activity and in hypochlorous acid production. These observations demonstrate that tenidap has properties that set it apart from conventional NSAIDs and suggest that it may be a particularly useful agent in the treatment of inflammatory rheumatic disorders.