The routes by which secretory proteins leave the pancreas have been studied during single-pass perfusion of the isolated cat pancreas with a physiological salt solution. The amounts of amylase and total protein appearing in pancreatic juice, venous effluent, and the exudate escaping from the surface of the gland (probably representing lymph) were measured during stimulation with secretin alone and together with bolus injections of acetylcholine. During stimulation with secretin alone, the amylase output in venous effluent was four times greater than in pancreatic juice or exudate. In contrast, most protein appeared in exudate, some in the venous effluent, and a very small amount in pancreatic juice. Acetylcholine transiently increased the output of both amylase and total protein in pancreatic juice to values that greatly exceeded those in venous effluent and exudate. After a delay of 10 min, it also increased the output of amylase and total protein in exudate, but had no effect on venous effluent. In conclusion, secretory proteins enter the venous circulation at a constant rate (i.e., not influenced by acetylcholine stimulation). Some also appear in exudate (lymph), the proportion of which is determined by stimulation. Whether the proteins in these two fluids and in pancreatic juice are derived from the same intracellular pool remains to be determined.