1. In dogs with chronic gastric and pancreatic fistulas, a liver extract meal adjusted to various pH levels ranging from 7.0 to 2.0, was introduced into the stomach and the increments in plasma secretin levels were correlated with the pH of the liver extract meal and pancreatic bicarbonate outputs. 2. The pH threshold for both bicarbonate secretion and secretin release was found to be about 4.5. With a stepwise decrease in the pH of the meal below pH 4.5, there were stepwise increments in the plasma secretin concentrations and pancreatic bicarbonate outputs. 3. Exogenous secretin, given in graded doses ranging from 0.03 to 2.0 clinical unit/kg per hr, increased the plasma secretin concentrations and bicarbonate secretion in a dose-dependent fashion. 4. These results indicate that the pH threshold for release of endogenous secretin is 4.5 and suggests that, at pH levels below 4.5, pancreatic bicarbonate secretion depends upon the duodenal acid load and is linearly correlated to an increment in plasma secretin concentrations. 5. It is concluded that endogenous secretin is a major determinant of pancreatic bicarbonate secretion after a meal. 6. Pancreatic protein secretion by intragastric liver extract meal was greatly increased both in experiments with liver extract meal, pH 4.0 or below, and I.V. infusion of secretin at a dose of 0.12 u./kg per hr. It is questioned, however, whether this effect of secretin is physiological.