The authors investigated the role of activated perilobular, not periacinar, pancreatic stellate cells, in fibrogenesis in chronic pancreatitis, based on the distribution of myofibroblasts. Twenty-four patients with clinically diagnosed chronic alcoholic pancreatitis were studied histopathologically, immunohistochemically and quantitatively. In all cases, fibrosis was patchily distributed in the perilobular, or interlobular, areas, accompanied by a cirrhosis-like appearance; it had extended into the intralobular area in advanced cases. Seven patients had a massive or confluent loss of exocrine tissue, resulting in extensive interlobular fibrosis; the more extensive the interlobular fibrosis, the smaller the lobules. Immunoreactivity to alpha-smooth muscle actin, a myofibroblast marker, was found mostly in the same areas of the fibrosis, mainly the interlobular, and less often the periacinar, areas; the average percentage area of perilobular myofibroblasts was significantly higher than that of periacinar myofibroblasts in 20 randomly selected lobules (P > 0.001), in which the average value for the former was 38.03% (range: 13.54-61.32%; SD, 13.8%) and that for the latter was 4.85% (range 0.90-9.57%; SD, 2.22%). Fibrosis also immunostained positive for collagen types I and III. In conclusion, activated perilobular, not periacinar, pancreatic stellate cell contribute to fibrogenesis in chronic pancreatitis.