Background/Aims: Whether meal-related symptoms such as postcibal epigastric fullness and discomfort are caused by hypotonic gastric expansion or gastric hypertension is unknown. This study investigated whether symptoms in healthy individuals in response to gastric distention are produced by gastric expansion or by an increase in intragastric pressure. Methods: Increasing gastric distentions (for 5 minutes at 5-minute intervals) at fixed pressure levels (in 2-mm Hg increments) and at fixed volume levels (in 200-mL increments) were performed in 10 healthy subjects per group; perception was measured on a 0-6 scale. Distentions were performed during intravenous infusion of saline (basal) and during gastric relaxation by intravenous administration of glucagon (4.8-μg/kg bolus plus 9.6 μg · kg-1 · h-1 infusion). Results: The same distending pressures tested produced 30% ± 9% larger intragastric volumes and 80% ± 44% higher perception scores when the stomach was relaxed by glucagon (P < 0.05 vs. basal for both). In contrast, the same distending volumes tested produced 25% ± 7% lower intragastric pressures and 21% ± 12% lower perception scores when the stomach was relaxed (P < 0.05 vs. basal for both). Conclusions: Epigastric symptoms in response to gastric distention are influenced by both the intragastric pressure and the intragastric volume. © 1995.