These studies were undertaken to assess the effects of chronic administration of cerulein plus secretin, every 8 h for 10 days on fluid, protein, and somatostatin-like immunoreactivity (SLI) outputs in rat pancreatic juice. Pancreatic secretion was studied with conscious, cannulated rats, during infusion of precollected pancreatic juice to the rat intestine. Volume output reached a plateau of 5.2 ml/210 min after 3 days of treatment. Protein secretion steadily increased up to 218 mg/210 min after 5 days, decreased to 118 mg/210 min by day 7, and rose again to 281 mg/210 min after 10 days. The SLI release increased stepwise with a first plateau after 3 days at 493 ng/210 min; values between 983 and 562 ng/210 min were observed between days 4 and 7 with a third plateau at 1,887 ng/210 min between days 8 and 10. Peak levels of volume and protein occurred between 30 and 90 min following each daily stimulation. In the early days SLI output reached its peak 3.5 h after stimulation, whereas at the end of treatment, synchronous secretion of protein and SLI was observed. These data indicate that important modifications occur in the rate of secretion of protein and SLI in the pancreatic juice in the course of chronic administration of cerulein plus secretin.