Sjögren's syndrome (SS) is characterized by exocrine gland destruction associated with lymphocytic infiltrations and chronic autoimmune antigen-driven responses against the intracellular Ro/SSA and La/SSB ribonucleoproteins. Epithelial cells, which are the main targets of autoimmune responses, appear to have a central role in the pathogenesis of SS. In recent years we have presented evidence indicating that salivary gland epithelial cells (SGECs) of SS patients are inherently capable of functioning as antigen-presenting cells. Recently, a novel, cell-free mechanism of antigen presentation has been identified. This mechanism involves exosomes, which are small (30–200 nm) membrane vesicles of endosomal origin secreted by a variety of cell types, such as reticulocytes, B lymphocytes and dendritic cells. In the present study we investigated the capacity of cultured SGEC lines established from SS patients and disease controls to release exosomal vesicles that contain intracellular ribonucleoproteins. Membrane vesicles were isolated by differential centrifugation from SGEC culture supernatants and their nature was confirmed by electron microscopy. Cultured SGECs from patients and controls secreted significant amounts of exosomal vesicles, in a manner largely indistinguishable from other exosome-secreting cells. Exosome release was not associated with apoptosis or other cellular destruction processes. SGEC-derived exosomes were found by Western blot analysis to contain Ro/SSA, La/SSB, and Sm ribonucleoproteins. Our results indicate that SGECs are capable of secreting exosomes. This mechanism may represent a pathway through which intracellular epithelial antigens are exported and subsequently presented to the immune system. In this context, exosomes produced by epithelial cells may have a role in the pathogenesis of SS.