SummaryPancreatic juice was collectedin vivofrom control and reserpine‐treted rats after stimulation with pilocarpine (0.2 mg/100 g body weight), dopamine (6‐7 mg/100 g body weight), caerulein (90‐100 pmole total dose) or with a combination of caerulein and secretin (6 u/100 g body weight) and the volume, amylase, bicarbonate and chloride outputs were compared. The results indicate that the secretory response to the three secretagogues was significantly reduced in the drug treated animals. Thus, the volumes of pancreatic juice were 57.0, 60.5, and 15.7% of those obtained in control rats after stimulation with, respectively, pilocarpine, dopamine, and caerulein. Amylase output was 63.8, 67.1, and 21.0% and bicarbonate output was 29.9, 46.8, and 6.2% of those observed in untreated rats after the same stimulants. Fluid secretion increased in the treated animals to 71.3% of that of controls when both caerulein and secretin were administered together and amylase output became greater than in control rats (151%). However, bicarbonate output was still 55.2% of that of controls with this combined stimulation. It is concluded that chronic reserpine administration impairs exocrine pancreatic secretion and that this effect involves both the acinar and ductal portions of the gland. This impairment involves the physiologic responses of these two segments of the glandular epithelium to both neural and hormonal stimulants. These findings suggest that the exocrine pancreatic disturbance in reserpine‐treated rats may be similar to that observed in cystic fibrosis (CF), and because the treated rat has been proposed as a model for the human disease, they suggest the use of this model as a test system for the study of the pancreatic secretory abnormality in CF.SpeculationRats treated in a chronic fashion with reserpine secrete significantly smaller amounts of fluid, amylase, and bicarbonate in pancreatic juice than control animals, whether secretion is elicited by hormonal or neural stimulants. The abnormality in exocrine pancreatic function induced by the drug treatment involves, therefore, the acinar and ductal segments of the gland and is similar to the alteration seen in patients with CF.