Sjögren's syndrome (SS) is a chronic autoimmune exocrinopathy that is characterized by periductal mononuclear cell infiltrates in the affected exocrine glands. Epithelial cells are thought to play an important pathogenetic role, as suggested by the occurrence of infiltrating lesions in various epithelial tissues (described as autoimmune epithelitis) as well as the increased epithelial expression of several inflammatory proteins in the histopathologic lesions of patients. In the recent decade, the application of long-term cultured nonneoplastic salivary gland epithelial cell (SGEC) lines has permitted the more explicit analysis of the role of these cells in SS pathophysiology. In such studies, cultured SGEC have been demonstrated to express constitutively or inducibly various molecules that are implicated in innate and acquired immune responses, a fact that underscores the inherent capacity of these epithelial cells to induce and promote chronic inflammatory reactions. Furthermore, the parallel analysis of SGEC lines obtained from SS patients and disease controls has revealed the significantly increased constitutive expression of several molecules in cells derived from SS patients. This fact strongly suggests the operation of intrinsic activation mechanisms in the epithelia of patients and further supports the active participation of epithelia in SS pathogenesis.