Abstract.The effect of serum inhibitors on determinations of collagenolytic activity in culture fluids of healthy (G.I.=0) and mildly inflamed (G.I.=1) gingival tissue was studied. Gingival biopsies obtained at the beginning of the experimental gingivitis period (G.I.=0) and after approximately three weeks of no oral hygiene (G.I.=1) were subjected to tissue culture procedures previously utilized for the determination of collagenolytic activity. Inhibition of collagenase activity was evaluated by denaturing scrum inhibitors retained in culture fluid with sodium thiocyanate or by adding culture fluid from normal and inflamed tissues to a partially purified collagenase preparation.A decrease in collagenolytic activity was consistently demonstrable in untreated culture fluids of gingival tissue manifesting G.I.=1 as compared lo those exhibiting G.I.=0. When enzyme containing culture fluids were treated with NaSCN. however, no essential difference was detected. While culture fluids from healthy gingiva showed no inhibition of partially purified collagenase, culture fluids from tissues manifesting mild inflammation inhibited enzyme activity by approximately 60 %.A number of cell types associated with the periodontium have the ability to produce a specific collagenase. The results of this investigation suggest, however, thatin vitrodeterminations of collagenolytic activity in culture fluids of normal and inflamed tissues may be influenced by specific scrum inhibitors.