The three major phases in the secretory process in the exocrine pancreas (synthesis, intracellular transport, zymogen discharge) have been tested in vitro after changing circulating insulin levels in rats in vivo. One group of rats received a continuous infusion of glucose for periods up to 72 hours, which keeps blood glucose levels above 200 mg/100 ml and immunoreactive insulin (1RI) raised to 130 µU/ml. As a result of this treatment, amylase content in the pancreas increases by 25% while chymotrypsinogen and lipase show a comparable decrease. The rate of total protein synthesis increases by 40% after 48 hours of infusion. The basal and carbamylcholine stimulated discharge of newly synthesized proteins are not altered. The baseline discharge of amylase is increased significantly, while the discharge of lipase and chymotrypsinogen decreased below control levels. Similar results are obtained, if circulating insulin levels are raised by the application of glibenblamide (HB419) for a period of 24 hours. Protein synthesis increases by 26.5% and baseline discharge of amylase by 50%. In chronic alloxan diabetic animals the alteration of the exocrine pancreatic function depends on the severity of the diabetes and relates to circulating insulin levels. Animals with highest blood glucose levels and low or undetectable insulin concentrations show a disappearance of amylase from the exocrine pancreas and a depression of the rate of protein synthesis by 30%. The results suggest a direct effect of insulin on protein biosynthesis and zymogen discharge, most pronounced for amylase.