The endocrine pancreatic tissue from patients with severe primary chronic pancreatitis (n=6). secondary chronic pancreatitis due to duct obstruction by carcinoma (n=6) and non-diabetic, non-pancreatitic controls (n=4) was studied qualitatively and quantitatively using specific immunocytochemistry and electron microscopy. Grouping of variously sized islets in the sclerotic tissue (sclerosis islets), islet neoformation by ductuloinsular proliferation, and intrainsular fibrosis were the main qualitative findings. Immunocytochemical quantitation of the distribution of insulin (B), glucagon (A), somatostatin (D) and pancreatic polypeptide (PP) producing cells revealed a significant relative increase in the number of A cells and a decrease in the number of B cells of the sclerosis islets in primary chronic pancreatitis ((B-44.1+/-9.3%:A-38.3+/-2.4%:D-8.6+/-5.1%:PP-4.6+/-4.1%) as well as in secondary chronic pancreatitis B-38.0+/-14.3%:A-38.4+/-19.0%:D-9.1+/-5.8%:PP-14.5+/-23.4%) compared with controls (B-71.1+/-8.1%:A-24.3+/-5.5%:D-8.0+/-2.8%:PP-0.5+/-0.4%). The number of PP cells was significantly increased in primary chronic pancreatitis only. It is suggested that scarring of the exocrine pancreas affects islet composition, probably by impairment of the local circulation and of glucose diffusion, thus leading to reduction of the number and glucose sensitivity of B cells. The hyperplasia of A and PP cells appears to be a secondary phenomenon due to the loss of B cells.