In conscious chronic gastric and pancreatic fistula dogs (Thomas cannula), secretin was perfused for three hours with a submaximal (GIH, 1.0 C.U./kg.) and a maximal dose (GIH, 8.0 c.u./kg.), according to the following schedule: 1. First hour submaximal stimulus; 2. second hour maximal stimulus; 3. third hour submaximal stimulus. The alkaline and protein components of pancreatic secretion were analyzed in 20-minute sample collections thoughout the three hours. The same protocol was followed in anesthetized dogs subjected to a mind line laparotomy. A biopsy of the pancreatic gland was taken before (control) and at the end of each perfused dose. The secretion showed a significant increase of protein concentration and output when passing from the maximal to the last submaximal secretin perfusion dose. These findings correlated well with the piling up of zymogen and prozymogen granules in the apical zone of the acinar cells during maximal secretin perfusion, with their subsequent discharge into the acinar lumen upon abrupt reversal to the initial secretin submaximal dose. The study confirms that secretin influences pancreatic protein secretion and indicates in addition, that pharmacologic doses of the hormone, have the capacity to block acinar cell zymogen granule release.