Sjogren syndrome (SS) is an autoimmune disease characterized by diffuse lymphoid cell infiltrates in the salivary and lacrimal glands, resulting in symptoms of dry mouth and dry eye due to insufficient secretion. Although it has been assumed that a combination of immunologic, genetic and environmental factors may play a key role on the development of autoimmune lesion in the salivary and lacrimal gland, little is known about the disease pathogenesis. We have identified the 120 KD -fodrin as an important autoantigen on the development of SS in both animal model and SS patients, but the mechanism of -fodrin cleavage leading to tissue destruction in SS remains unclear. Tissue-infiltrating CD4+ T cells purified from the salivary glands bear a large proportion of Fas ligand and the salivary gland duct cells possess apoptotic receptor Fas. Anti-Fas antibody-induced apoptotic salivary gland cells results in specific -fodrin cleavage to the 120 KD fragment in vitro. Preincubation with a combination of calpain and caspase inhibitor peptides could be responsible for inhibition of the 120 KD -fodrin cleavage. Thus, an increase in apoptotic protease activities may be involved in tha progression of -fodrin proteolysis and tissue destruction in the development of SS.