To investigate the effects of endogenous insulin on pancreatic exocrine secretion in humans, we evaluated the pure pancreatic juice obtained by endoscopic cannulation of the main pancreatic duct in 21 healthy subjects (14 men and seven women). Samples of pancreatic juices were collected after intravenous injection of either glucose (50%, 40 ml), secretin (0.25 CU/kg), and cholecystokinin-8 (CCK) (40 ng/kg), or a combination of glucose, secretin, and CCK in six 5-min periods. The responses of plasma glucose, insulin, and C-peptide to intravenous administration of glucose were measured. After infusion of glucose, the plasma insulin and C-peptide levels were significantly increased and remained at high levels during 30-min experiments, intravenous administration of secretin and CCK resulted in significant increases of pancreatic secretion including volume, bicarbonate, and protein output. When glucose was simultaneously administered with secretin and CCK, pancreatic secretion was significantly increased, more than the effects achieved by the secretin and CCK. However, glucose alone did not increase basal pancreatic secretion. These observations suggest that endogenous insulin intensifies pancreatic secretion stimulated by secretin and CCK in humans.