The activity of human gingival collagenase was inhibited by an inhibitor found in an extract of human teeth. This inhibitor, denoted Human Dental Collagenase Inhibitor, was partially purified and found to selectively inhibit human skin and gingival collagenase, as well as tadpole collagenase, but not the bacterial collagenase (Clostridium histolyticum). On the basis of gel filtration analysis we determined that the inhibitor has an apparentmolecular weight of approximately 12,000 daltons, similar tothat reported for other tissue collagenase inhibitors.