In man, only little is known about the site of origin of satiety signals within the gastrointestinal tract. Therefore, it was the aim of this study to examine the role of the stomach and the small intestine as a source of satiety signals. 8 overnight fasted healthy volunteers received intraduodenal (100 or 200 ml/h) or intragastric (100 ml/h) infusions of a mixed liquid diet (Biosorb) or iso-osmolar saline, respectively. 20 minutes after start of the infusion, standardized mini-sandwiches and water were presented and food intake was recorded for the ensuing 90 minutes. During both rates of intraduodenal nutrient infusion, cumulative food intake was identical to that during saline infusion. However, during intragastric nutrient infusion, cumulative food intake was significantly reduced compared to saline infusion (30 +/- 1 vs. 36 +/- 2 sandwiches; p less than 0.05). These data indicate that food consumption in man is reduced, if initiation of eating is preceded by nutrient administration into the stomach, but not into the duodenum. This effect does not appear to be mediated by gastrin, since plasma gastrin levels were not different during gastric and duodenal nutrient administration. In conclusion, the results of this study suggest that the generation of satiety signals in man is dependent on the presence of food in the stomach. Food only in the duodenum has no effect, although synergistic gastric and intestinal mechanisms can as yet not be excluded.