Of 12 patients operated on for intractable pain from chronic pancreatitis, only the three with adequate preoperative insulin reserve were selected to undergo islet-cell replantation after subtotal pancreatectomy. Fourteen, nine, and four months postoperatively, they require no therapy with insulin. Since most techniques for obtaining islet cells have been performed with normal pancreata, chronic pancreatitis was produced in ten dogs by ligating the main and accessory pancreatic ducts. These dogs 162.6 +/- 15.8 days later underwent total pancreatectomy. The scarred pancreatic fragments were dissociated with collagenase for 20 minutes in five dogs or subjected to two intermittent digestions of ten minutes in the other five dogs and were autotransplanted to the liver. One dog from each group became normoglycemic within one week of replantation, and their percent per minute decreases of serum glucose level were 2.72 and 3.46, respectively. Our experimental and clinical data suggest that (1) present techniques for dissociating fibrotic tissue are unsatisfactory and lead to a very low yield of islet cells; (2) postoperative assessment of islet-cell function involves complicated invasive procedures (portal and hepatic vein cannulation) to determine accurately the source of insulin; and (3) careful preoperative evaluation of beta-cell function is needed.