The present study was performed to determine the time-dependent effects of chronic administration of maximal doses of cerulein on the secretory function of the rat pancreas. Four groups of rats, one treated with 0.9% NaCl (control) and the others with cerulein (2, 5, and 10 ÎĽg/kg twice a day ip, respectively) were used. After a treatment period of 15, 30, or 60 d, eight rats were taken from each group, the pancreatic bile duct was surgically cannulated, and the pancreatic juice was collected after CCK or secretin stimulation. Then the rats were killed and the pancreas was removed and weighed. Administration of 2 ÎĽg/kg of cerulein for 15 d induced a significant increase (p<0.05) in the volume of pancreatic juice in response to hormonal stimulation. The enzyme and bicarbonate outputs increased only in response to CCK, not to secretin. The above-mentioned increases are significant only when related to body weight, not to pancreatic weight. There was good correlation between pancreatic weight and the increase in the secretory parameters. The secretion pattern was not significantly modified by higher doses of cerulein nor by longer duration of treatment. We conclude that 1) increase in pancreatic secretory function induced by 2 ÎĽg/kg of cerulein is not enhanced by higher doses of peptide and 2) the functional capacity of the acinar cells is not affected by the length of treatment. These data are of interest as experimental backing to therapeutic use of CCK-like peptides in pancreatic exocrine insufficiency.