The expression of beta 2-microglobulin (beta 2m), class II major histocompatibility complex (MHC) antigens (HLA-DP, -DQ, -DR) and the interleukin 2 receptor (IL-2R) on resident and infiltrating cells in labial salivary glands of patients with Sjögren's syndrome (SS) was studied using an immunoperoxidase technique based on staining with monoclonal antibodies. The progression of the inflammatory process was accompanied by increasing numbers of immunocompetent cells as well as glandular epithelial cells expressing beta 2m and class II MHC antigens. Up to 60% of the infiltrating lymphocytes were DQ- and DR-positive while fewer cells stained for DP antigen. Glandular epithelium (acinar and ductal cells) stained for products of all three HLA-D subregions but with varying degrees of expression following the pattern DR greater than DP greater than DQ related to the severity of inflammation. A minor portion of the infiltrating lymphocytes expressed IL-2R. These findings emphasize the potential importance of epithelial expression of class II antigens in the local activation of T lymphocytes in salivary gland lesions of SS patients. They also indicate that differences may exist in this respect between T-cell reactions restricted by different class II MHC-encoded gene products.