T he autologous mixed lymphocyte reaction (AMLR) measures the response of peripheral blood T cells to antigens present on the surface of non-T cells. The AMLR was studied in 25 patients with Sjögren's syndrome (SS). The AMLR was decreased in 15 of 25 (60%) of patients with SS (5,272 +/- 6,738 cpm vs. 14,396 +/- 10,092 cpm for the normal controls, P < 0.001). The AMLR was decreased in 8 of 15 patients with only glandular disease who were not on any systemic medications. Patients with SS and associated disease had lower responses than patients with SS alone. Two patients with pseudolymphoma had absent response. The decreased AMLR correlated with a decreased response to concanavalin A, suggesting a possible abnormality of a T cell subpopulation. There was no correlation between the decreased AMLR and age, focus score, serum immunoglobulin concentration, the titer of antilymphocyte antibody, or phytohemagglutinin response. In allogeneic MLR, SS non-T cells and macrophages stimulated normal allogeneic T cells less well than normal non-T cells and macrophages, suggesting a possible abnormality in the cells that stimulate in the cells that stimulate in the allogeneic MLR.