The specific cellular immune response to the partially purified pancreatic antigen was studied by the peripheral blood lymphocyte proliferation assay in patients with chronic pancreatitis, Sjögren's syndrome, and primary biliary cirrhosis. A significant positive result (stimulation index > 2.0) was observed in 7 of 21 patients with idiopathic chronic pancreatitis (33%; P < 0.05), 6 of 7 patients with Sjögren's syndrome-associated chronic pancreatitis (86%; P < 0.0005), and 6 of 11 patients with Sjögren's syndrome (55%; P < 0.01), compared to normal controls whose stimulation index was 0.94 +/- 0.28 (mean +/- SD; n = 14; range, 0.56-1.60). On the other hand, patients with alcoholic chronic pancreatitis (17%; n = 12), stone-related chronic pancreatitis (0%; n = 7), primary biliary cirrhosis-associated chronic pancreatitis (33%; n = 3), primary biliary cirrhosis (0%; n = 4), systemic lupus erythematosus (17%; n = 6), and autoimmune thyroiditis (0%; n = 6) showed no significant difference from normal controls. Furthermore, in patients with idiopathic chronic pancreatitis who had positive results, a lymphocyte proliferative response to the pancreatic antigen was observed in T cells, especially in the CD4+ T cell subpopulation. These results suggest that the pancreatic antigen plays a role in the pathogenesis of a part of idiopathic chronic pancreatitis and Sjögren's syndrome in association with T cell responses and, also, suggest that autoimmunity may be a possible etiological factor in chronic pancreatitis.