Labial salivary glands biopsies (LSG) performed to support clinical anomalies suggestive of Sjögren's syndrome (SS) sometimes fail to confirm the diagnosis. Here we investigated whether epithelial activation markers could provide further information. Frozen cut sections of LSG from 40 patients, including 23 confirmed SS, were examined in immunofluorescence for the expression of HLA class II molecules, the protector of apoptosis bcl-2, the intercellular adhesion molecule 1 (ICAM-1) and secretory component (SC). Class II molecules were highly expressed on epithelial cells in SS patients (DR > DP > DQ). Bcl2 was expressed in infiltrating cells which were more numerous in the group of SS patients. ICAM-1 was present on endothelial and infiltrating cells of a few patients in both groups. Epithelial cells produced SC in 83% of SS patients samples vs four cases of non-SS patients (P = 0.0002). Investigation of the expression of SC on glandular epithelial cells could therefore be proposed as a marker of SS.