Collagenases (EC 3.4.24.3) from human skin, rat skin and rat uterus were inhibited by the chelating agents EDTA, 1,10-phenanthroline and tetraethylene pentamine in the presence of excess Ca 2+, suggesting that a second metal ion participates in the activity of the enzyme. Collagenase inhibition by 1,10-phenanthroline could be both prevented and reversed by a number of transition metal ions, specifically Zn 2+, Co 2-, Fe 2+ and Cu 2+. However, Zn 2+ is effective in five-fold lower molar concentrations ( 1 · 10 −4 M ) than the other ions. Furthermore, Zn 2+ was the only ion tested able to prevent and reverse the inhibition of collagenase by EDTA in the presence of excess Ca 2+ Atomic absorption analysis of purified collagenase for Zn 2+ showed that Zn 2+ was present in the enzyme preparations, and that the metal co-purifies with collagenase during column chromatography