To study in healthy subjects the relationship between gastric sensations/perception and motility during gastric distension and the effects of duodenal nutrients, a flaccid gastric bag was distended in the proximal stomach with air at 100 ml/min while the duodenum was perfused (1 ml/min) with isotonic saline, hypertonic saline, glucose (1 kcal/ml), maltodextrin (2 kcal/ml), and 10% (1 kcal/ml) and 20% lipid (2 kcal/ml). Intragastric pressure was recorded continuously, and the subjects were asked to report gastric sensations. Compared with isotonic saline, all infusions significantly decreased gastric tonic and phasic pressure activity during gastric distensions and, with the exception of 20% lipid, caused fullness and discomfort during distensions to occur at larger volumes associated with lower intragastric pressures. Maltodextrin and 20% lipid changed fullness during distensions into a meal-like sensation. Only 20% lipid significantly increased the incidence of nausea. In conclusion, the sensory responses to gastric distension are modified by duodenal nutrients. Different nutrients result in different responses, but the responses obtained cannot be explained by changes in gastric pressure activity.