Alpha-1-antitrypsin (AAT) is a serum protease inhibitor, with a well established role in bodily defense against destructive inflammatory disease. In order to investigate the role of this protease inhibitor in the periapical lesions, 13 patients were investigated. Serum alpha-1-antitrypsin levels of 13 patients were 871.8 +/- 73.6 mg/dl whereas 296.6 +/- 32.6 mg/dl in the control group. Difference was important between both groups (P less than 0.01). Alpha-1-antitrypsin levels were 40.2 +/- 13.7 mg/dl in the cyst fluid. Although the alpha-1-antitrypsin levels in the patients serum were elevated, it was not found in sufficient levels in the cyst fluid. This results suggest that, the regulation of proteolytic activity afforded by AAT, plays an important role in the pathogenesis of periapical lesions.