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To evaluate the clinical significance of a swollen main duodenal papilla and the associated immunohistopathologic findings in patients with autoimmune pancreatitis (AIP).Seventeen consecutive patients with AIP registered between April 2001 and October 2005 who underwent both endoscopic retrograde cholangiopancreatography and endoscopic biopsy were enrolled in this study. The endoscopic features, stromal inflammatory cell infiltrate (SICI), and results of immunohistochemical examination of the duodenal papilla using IgG4, CD3, and CD79a antibodies were retrospectively reviewed. These findings in the AIP patients were compared with those in 12 patients with chronic alcoholic tumor-forming pancreatitis (CAP). The numbers of cells in the SICI and of IgG4-positive plasma cells per high-power field were counted in all the histopathologic specimens.A swollen main duodenal papilla was observed in 11 (11 [64.7%]/17) patients with AIP and 4 (4 [33.3%]/12) patients with CAP (P < 0.05). Resolution of the swollen main duodenal papilla was observed in all of these 11 patients with AIP (11 [100%]/11) in response to treatment with corticosteroids. On the other hand, the 6 patients without elevated serum IgG4 or a swollen duodenal papilla, but with a swollen pancreas, improved even without corticosteroid treatment. The number of cells in the SICI in the AIP patients was significantly higher than that in the CAP patients. Although in 13 of 17 AIP patients, infiltration by IgG4-positive plasma cells was detected in the duodenal papilla, no such significant infiltration of the duodenal papilla by IgG4-positive plasma cells was observed in the patients with CAP (P < 0.05). More predominant T-cell infiltration of the duodenal papilla was recognized in the AIP patients than in the CAP patients (P < 0.05).These results suggest that a swollen main duodenal papilla with IgG4-positive plasma cell and T-cell-dominant infiltration and an abundant stromal cell infiltrate are characteristic findings in AIP. We suggest that these findings may be valuable adjuncts to the diagnosis of AIP as well as for selecting suitable candidates for corticosteroid therapy.