The evidence for the participation of signals from the gastrointestinal tract in hunger and satiety is reviewed. Various methods of subjecting only certain portions of the gastrointestinal tract to food are described including sham feeding, crossing of the intestines of two animals, and intragastric, intraduodenal and intravenous feeding. These methods have revealed that animals eat more when ... [Show full abstract] only the mouth is exposed to food, but consume less when food enters the stomach directly and still less when feeding themselves intravenously. The role of the stomach in satiety is discussed in relation to the results of the many experiments in which intragastric loads were administered. These experiments generally revealed that gastric loads suppressed intake in proportion to their caloric value, but that compensation was not precise. A similar analysis is made of the role of the intestines in satiety. These studies present evidence for osmoreceptors and glucoreceptors, distention, and pressure, all of which may participate in satiety. The numerous effects of vagotomy on food intake are reviewed and an attempt is made to separate afferent from efferent effects and vagal effects from nonspecific surgical injury. The role of other afferents is explored. A brief survey of the most recent studies on humoral factors indicates that cholecystokinin is probably acting as a satiety agent, but its mode of action remains unknown. The changes in the gastrointestinal tract that accompany an increase or decrease in food intake reveal adaptive changes that occur in the organ. The evidence for gastrointestinal factors in satiety of the suckling animal is presented. Finally, a hypothesis is presented in which the various factors that bring a meal to an end are included. Preabsorptive satiety may consist of multiple factors which probably include signals from osmoreceptors and possibly other chemoreceptors in the upper small intestine. The signals from these receptors are neural while other products of digestion stimulate the release of humoral agents, such as cholecystokinin, which may act locally, in the liver, or on the central nervous system. Stretch or distention of the intestines at various locations may also contribute to preabsorptive satiety.