1. A method for the isolation and vascular perfusion of the porcine pancreas and duodenum was developed. 2. The oxygen consumption of the whole preparation was similar to that of the pancreas alone, and since the duodenal arteriovenous oxygen deficit was similar to that of the total preparation, it was concluded that the duodenum respired adequately. 3. The duodenum rapidly absorbed luminally administered radioactive glucose, and this absorption was strongly inhibited by ouabain and phloridzin. 4. The duodenum secreted secretin rapidly in response to hydrochloric acid, but did not respond to any other luminal stimuli, including lipids, proteins, carbohydrates and bile. Neither was secretin release stimulated by intra-arterially injected acetylcholine. 5. By gel permeation chromatography the release immunoreactive secretin behaved identically to pure natural secretin, indicating that the tissue form and the circulating form have identical molecular size. 6. It is concluded that this model offers an unique opportunity to study the endocrine secretion of the duodenum.