1. Differentiation between the secretory effects of pure natural cholecystokinin-pancreozymin (CCK-PZ) and those of synthetic secretin was studied in the isolated pancreas of the rat perfused with a standard solution containing both Ca2+ and HCO2-, a Ca2+ deficient solution, or a HCO3-deficient solution. 2. Secretin induced a dose-dependent increase in the flow of pancreatic juice and a slight but definite increase in amylase output which was also dependent upon the dose of secretin. 3. The increase in the flow of pancreatic juice, induced by continuous stimulation with secretin (5 Ivy dog m-u./ml.), was completely abolished during perfusion with a CHO3- deficient solution, but was only slightly suppressed during perfusion with a Ca2+-deficient solution. 4. The increase in flow, induced by continuous stimulation with CCK-PZ (5 Ivy dog m-u./ml.), was partly affected by the deprivation of HCO3-, but was strongly inhibited by the deprivation of Ca2+. The CCK-PZ-induced amylase output was not affected by the deprivation of HCO3-, but was significantly inhibited by the deprivation of Ca2+. 5. The present results favour the view that CCK-PZ acts on the acinar cells to increase both amylase output and juice flow, whereas secretin acts on centro-acinar and terminal duct cells to increase mainly juice flow.