Chronic pancreatitis is a regressive disease, sometimes progressing to the point of insufficient secretion from both the exocrine and the endocrine pancreas. Functional decline is matched by morphological changes in the parenchyma and stroma. Acinar cells redifferentiate to produce tubular complexes and degenerate, resulting in a larger proportion of ductular cells than normal. The decrease in parenchyma is more than made up for by an increase in stroma. Characteristically, marked fibrosis occurs. Chronic inflammatory cells are prominent, frequently occurring as clusters. The large pancreatic ducts are altered as well. They may be denuded of their epithelium, eliminating the barrier that normally exists. Plasma cells and inflammatory cells in their walls contribute to the extra components that are found in pancreatic juice. Pancreatic stones, consisting of calcium carbonate precipitated in an organic matrix, may form in the ducts. Chronic inflammatory cells cluster around nerves in and around the pancreas, inducing damage to the perineurium and eventually affecting nerve fibers. This direct damage, coupled with abnormal access of foreign substances to the interior of the nerves due to lack of the perineurial barrier, may provide a partial explanation for the chronic pain that is associated with the disease.