Autoimmune pancreatitis (AIP), a recently defined disease of unknown etiology, is characterized by inflammatory infiltrates in the pancreas with conspicuous involvement of the ducts. The disease clinically manifests in humans as epigastric pain, weight loss, and jaundice. This report describes the development of a novel animal model of this disease in the rat, which we have termed experimental autoimmune pancreatitis. Adoptive transfer of amylase-specific CD4(+) T cells was able to confer pancreatitis to naive syngeneic recipient animals. No treatments before the adoptive transfer of T cells were necessary for disease to ensue, and the severity of disease was proportional to the number of T cells administered. The pancreatic lesions of rats with experimental autoimmune pancreatitis were characterized histologically as overwhelmingly lymphocytic with occasional plasma cells, neutrophils, and mast cells. Acinar tissue destruction and ductular inflammation were common features, with less frequent involvement of larger ducts. Immunohistochemical analysis revealed the presence of CD4(+) T cells in large numbers as well as CD8(+) T cells, macrophages, and dendritic cells. Expression of MHC I and MHC II also increased at the site of the lesion. Clinically, the disease manifested as either failure to gain weight at a rate concomitant with control animals or as outright weight loss. Thus, administration of activated CD4(+) T cells specific for the pancreatic enzyme amylase can induce pancreatitis in the rat in a manner that is reminiscent of human AIP.