The influence of the endocrine pancreas on exocrine pancreatic function was studied in rats made diabetic by administration of streptozotocin. In normal urethan-anesthetized rats the C-terminal octapeptide of cholecystokinin (CCK-8) stimulated the rate of flow and rates of amylase and trypsinogen release from the pancreas; the proportions of the two enzymes did not change with repeated stimulation. In diabetic rats CCK-8 (0.3-1.2 nmol . kg-1 iv) stimulated significantly greater increases in trypsinogen output and rate of flow compared with normal animals. In contrast, amylase responses to CCK-8 were significantly depressed in diabetic rats. There were no differences between normal and diabetic rats in the flow and total protein responses to exogenous secretin. The present results indicate that the effects of insulin deprivation on relative rates of enzyme synthesis are also expressed in the secretion of the intact pancreas in vivo. These results also raise the possibility that in the normal intact gland there may be nonparallel release of enzymes at different rates of secretion depending on the relative secretory activities of cells in the immediate vicinity of the islets of Langerhans and those distant to the islets.