As tissue cultures, rabbit bone, skin and non-gravid uterus synthesise inhibitors of collagenase (EC 126.96.36.199). An assay for the inhibitors is described and their action on collagenase from different tissue sources demonstrated. Evidence for the involvement of the tissue inhibitors of collagenase in the latency of the enzyme in culture media is presented. Latent collagenase was activated by treatment with 4-aminophenylmercuric acetate, and then reacted with the inhibitors to form inactive complexes with properties similar to the naturally occurring latent enzyme forms. The associated changes in molecular weight are detailed, and discussed in relation to the observations of other workers concerning the extracellular control of collagenase activity.