The release of insulin, glucagon and somatostatin from islets isolated by microdissection, and islets isolated by aid of different duration of collagenase digestion from pancreases with exocrine atrophy was assessed. Prior collagenase digestion caused an increased release of insulin and glucagon, but not somatostatin; also, the non-suppressibility of glucagon secretion despite high glucose concentration in the medium was characteristic for those islets. Additional data suggest that in the absence of intrinsic pancreatic proteases the nature of the damage conferred by collagenase to islet B- and A-cells is different. In the light of action of epinephrine, an inhibitor of insulin secretion, possible mechanisms responsible for disturbed hormone release in the presence of proteolytic enzymes are discussed.