OBJECTIVES: Numerous patients with Papillon-Lefevre syndrome (PLS) express a severe periodontal inflammation that results in prema-ture loss of deciduous and permanent teeth. The plasminogen activat-ing (PA) system is involved in physiological and pathological processes including epithelial healing, extracellular proteolysis and local in-flammatory reactions. The aim of the study was to explore a possible role of the PA system in patients with PLS. MATERIAL AND METHODS: Samples of gingival crevicular fluid (GCF) were collected from areas with gingival infection in 20 patients with PLS and in 20 healthy controls. The concentration of tissue plasminogen activator (t-PA) and inhibitor (PAI-2) was measured with ELISA. RESULTS: The median level of PAI-2 was significantly higher (p < 0.01) in PLS pa-tients than in the controls, while the median value of t-PA did not dif-fer between the groups. No difference in t-PA or PAI-2 levels was found regarding age, gender or presence of active periodontal disease. CONCLUSION: The findings indicate an atypical activity of the PA system with a disturbed epithelial function in PLS patients, suggesting that the periodontal destruction seen in patients with PLS is secondary to a hereditary defect in the defense system.