The effect of various intraduodenal alkaline solutions (0.1 M NaHCO3, 0.1 M Na2CO3 and 0.025 M NaOH) on exocrine pancreatic secretion and the release of two peptides, secretin and vasoactive intestinal polypeptide, was studied in anesthetized rats. The flow rate of the pancreatic juice was stimulated up to a maximum of 179, 158 and 180% and the protein output up to 181, 131 and 162% (compared with basal) after duodenal perfusion of, respectively, 0.1 M NaHCO3, 0.1 M Na2CO3 and 0.025 M NaOH. Maximum increases in portal plasma secretin concentrations of 143, 146 and 190% and maximum increases in VIP of 116, 155 and 147% after, respectively, intraduodenal 0.1 M NaHCO3, 0.1 M Na2CO3, and 0.025 M NaOH were found. In conclusion duodenal alkalinization in the rat produces a pancreatic exocrine secretory response that may be partially ascribed to the effect of secretin and VIP.