Monoclonal antibodies directed against T-cell subsets, B-cell subsets, and monocytes were used to characterize the cells infiltrating the salivary glands of patients with primary Sjogren syndrome (1 degree SS). Analysis of stained frozen tissue sections and lymphocyte suspensions derived from salivary glands revealed the majority of infiltrating cells to be T cells (reactive with antibodies SC1 and Leu 4) of the Leu 3a+ subset (greater than 70% reactive). Of particular interest, a high frequency of Ia+ T cells (up to 50% of T cells) and B cells reactive with antibody B532 (5-15% of infiltrating cells) were found in salivary gland lymphocytes (SGL) but not in peripheral blood lymphocytes (PBL) of the same patients. Our finding that the phenotype of SGL was significantly different from PBL emphasizes the need to characterize lymphocytes at the site of tissue destruction. In vitro functional assays demonstrated that the OKT4+ SGL exhibited T-helper activity but not natural killer, antibody-dependent cellular cytotoxicity, or cytotoxic T-lymphocyte activity. Of note, rheumatoid factor (IgM anti-IgG) was produced by SGL but not by the corresponding PBL. Our studies on SG-lymphocyte function represent an early step in elucidating the cellular and subcellular events responsible for this autoimmune disease.