The major histocompatibility complex (MHC) class II antigens have been reported to play an important role in antigen presentation to T cells and influence the susceptibility to several autoimmune diseases, including Sjögren's syndrome (SS). In this paper, an aberrant expression of MHC class II antigens, especially HLA-DR antigens, on salivary glands of SS is described. HLA-DR antigens were immunohistochemically detected on acinar and ductal epithelial cells of SS patients but not those of healthy controls. This expression was observed in proximity to the periphery of dense lymphocytic infiltrates but sometimes not associated with lymphocytic infiltrates. These results are consistent with recent findings of HLA-DR antigen expression on target organs of various autoimmune diseases. Finally, we discussed a pathogenic role of HLA-DR antigens, aberrantly expressed on target organs of SS.