This study was prospectively carried out in order to clarify if an aberrant expression of HLA-DR molecules could take part in the pathogenesis of chronic pancreatitis. Pancreatic specimens from 12 chronic pancreatitis patients and nine controls were examined. Strong HLA-DR expression was observed in 6/12 chronic pancreatitis patients and in 1/9 controls. Moreover, lymphocytic foci with large numbers of activated cells were found only in chronic pancreatitis. The four HLA-DR.sbd.patients had a marked increase of fibrous tissue with small portions of acinar tissue, whereas the six patients with strong positivity had the greatest dilatation and hyperplasia of the ducts. These findings are similar to those observed in immune diseases, such as thyroiditis and primary biliary cirrhosis (PBC), and suggest that autoimmune phenomena are involved in chronic pancreatitis.