OBJECTIVE To evaluate variables of the kininogen-kallikrein-kinin system (KKKS) simultaneously in plasma and saliva of patients with Sjögren's syndrome (SS). METHODS We studied a group of 20 female patients with SS aged 37-75 years, 7 with primary SS (SS1) and 13 with SS secondary to rheumatoid arthritis (SS2), and 20 healthy individuals. Total kininogen and high and low molecular weight kininogen (HKg and LKg, respectively) levels were evaluated by ELISA. The activity of plasma and tissue kallikreins was determined by enzyme activity on selective chromogenic substrates. RESULTS The plasma levels of total kininogen, HKg, and LKg, and the activity of plasma kallikrein observed in patients were not significantly different from controls. The tissue kallikrein-like activity in plasma and the active tissue kallikrein in saliva were significantly increased in patients with SS, whereas the total salivary tissue kallikrein activity in patients was not significantly different from controls. The concentration of protein in the saliva of patients was significantly increased, and a positive correlation between salivary protein levels and the active tissue kallikrein was observed. CONCLUSIONS Comparisons between the total and the active tissue kallikrein in saliva of patients with SS showed that most of the tissue kallikrein was in its active form. In addition, we observed a concomitant increase of the tissue kallikrein-like activity in plasma. These results suggest increased activation of the KKKS in plasma and saliva of patients with SS.