Total TIMP-1 concentration in whole saliva of periodontally diseased subjects, 137 +/- 67 ng/ml (mean +/- SD), was clearly lower (p < 0.001) than that of clinically healthy subjects, 273 +/- 145, and that of edentulous subjects, 332 +/- 121. On the contrary, both active [1.58 +/- 0.35 units/ml (mean +/- SD)] and total (2.08 +/- 0.25) collagenase activities in TIMP-1-free whole saliva of diseased subjects were significantly higher than the activities (0.14 +/- 0.14 and 0.50 +/- 0.27, respectively) in TIMP-1-free whole saliva of healthy subjects. Most of the total collagenase in whole saliva of healthy subjects consisted of procollagenase, while mainly active collagenase was present in whole saliva from patients with periodontal diseases. Significant reciprocal changes of TIMP-1 and collagenase levels, that is, increase in TIMP-1 concentration and decrease in collagenase activity, were observed after the initial therapy of periodontitis patients.