To evaluate the prevalence of autoantibodies against the b-islet cells (ICA) and the molecule of insulin (IAA) in the serum of patients with pancreatic adenocarcinoma (PA), we examined the sera of 36 newly diagnosed pancreatic adenocarcinoma patients for the presence of these antibodies, using an enzyme-linked immuno-assay method. These results were correlated with survival. Ten patients with insulin-dependent diabetes mellitus (IDDM) and 21 healthy volunteers were evaluated as age-matched controls. Twenty out of 36 (57%) PA patients were found to have detectable ICA autoantibodies and 17 (48%) PA patients had detectable IAA antibodies. Five out of 10 (50%) and 3 out of 10 (30%) IDDM patients had ICA and IAA antibodies, respectively. None of the healthy volunteers was positive for either of the autoantibodies examined. The difference was statistically very significant and the presence of high serum titers of both autoantibodies was associated with a worse outcome for these patients than for those without such autoantibodies. Our data suggest that the high incidence of diabetes mellitus in patients with PA may be attributed to the presence of these autoantibodies. Further clinical studies are needed to establish the above autoantibodies as prognostic markers of pancreatic cancer.