Sjögren's syndrome (SS) is an autoimmune exocrinopathy characterized by mononuclear cell infiltration and loss of parenchymal tissue in salivary and lacrimal glands. The mechanisms for these histologic alterations are not known. Apoptotic cell death, induced by the ligation of Fas (APO-1/CD95) with Fas ligand (FasL/CD95L) may be an explanation for the tissue damage seen in SS. Fas and FasL were detected in minor salivary glands from SS patients and healthy individuals using immunohistochemical methods. There was increased expression of both Fas and FasL in the patients. The ability of the Fas-FasL pathway to influence epithelial cell growth and survival was demonstrated in vitro using a human submandibular cell line. The presence of Fas receptor was demonstrated on the cells. Anti-Fas antibody triggered cell death. Cells were also grown in the presence of gamma-interferon (IFN-gamma). IFN-gamma induced an upregulation of Fas receptor expression and pre-treatment of cells with IFN-gamma led to enhanced anti-Fas mediated cell death.