To investigate mechanisms that may be important in the pathogenesis of Sjogren's syndrome (SS) we developed a protocol for the growth of salivary gland epithelial cells in culture. We examined the effect that viral infection has on the cellular location of the autoantigen La. Autoantibodies to La arc common in SS and it has been porposed that viral infection may result in cell membrane expression of La. Co-expression of MHC class II molecules in infected cells could lead to the presentation of La peptides to the immune system. Advcnovirus infection of salivary gland epithelial cells resulted in an altered nuclear staining of La. Treatment with interferon-y resulted in the expression of La in the cell cytoplasm and HLA-DR molecules at the cell surface. These findings suggest that a cytokine-driven mechanism may generate an autoimmune response to La in SS. Using the polymerase chain reaction (PCR) we tested salivary gland epithelial cell cultures for the presence of human herpesvirus-6 (HHV-6) and Epstein-Barr virus (EBV). Only HHV-6 was detected in 2 of 10 salivary gland epithelial cell cultures although the presence of HHV-6 was not associated with SS. Primary salivary gland cultures may prove useful as anin vitromodel to study mechanisms of autoimmunity in SS.