We studied interleukin 2 (IL-2) production both in the peripheral blood and the lung in patients with Sjögren's syndrome (SS). IL-2 production of the peripheral blood mononuclear cells (PBMC) was significantly impaired in patients with SS (P less than 0.001). The patients with extraglandular disease and with associated connective tissue disease were more defective in IL-2 production. The defect could not be attributable to culture conditions. Both OKT4+ and OKT8+ T cells were deficient in producing IL-2. However, impaired IL-2 production could be partly restored by either (1) adding PMA to the PHA-stimulated culture, or (2) supplementing indomethacin (IM) from the initiation of the culture, or (3) depletion of adherent cells from PBMC. Furthermore, SS T cells were more sensitive to PGE1 than normal controls. In contrast, the response of PBMC to IL-2 was not disturbed in SS. IL-1 production of SS PBMC was not defective although there seemed to be suppressive factor(s) produced by SS adherent cells. In addition, IL-2 production of SS pulmonary lymphocytes was also decreased, suggesting that IL-2 producing cells might not be sequestrated in the lung. These data suggest that qualitative T cell defects and suppressor macrophages might be responsible for defective IL-2 production in SS and that IL-2 deficiency may contribute to the disordered immunoregulation in SS.