This study examined the role of free radical-induced tissue damage and the antioxidant defense mechanism of saliva in periodontal disease. Antioxidant activity of saliva was compared in 20 healthy individuals and 17 patients with periodontal diseases. We measured the scavenging capacity of saliva against free radicals generated in vitro by electrolysis, xanthine-xanthine oxidase, or stimulated polymorphonuclear leukocytes. Total protein content and total antioxidant activity of saliva were also determined. The results indicate that stimulated saliva of healthy individuals is significantly more effective (40-50%) than that of patients with periodontal diseases in scavenging a wide variety of free radicals generated in vitro. Under these conditions it appears that the total antioxidant activity of saliva is significantly decreased in these patients despite the fact that the levels of the three main antioxidants (uric acid, ascorbic acid, and albumin) are not significantly affected. We conclude that periodontal diseases are associated with an imbalance between oxidants and antioxidants in favor of the former due to both an increase in free radical production and a defect in the total antioxidant activity of saliva.