Background: Gastric distention contributes to meal termination. There is little research on the neural correlates of gastric distention by food. To date, neural measures have not been obtained concurrently with measurements of gastric distention.Objectives: 1) To study how offering a small versus a large water load following a standardized nutrient load affects gastric distention over time. 2) To assess associations between satiety experiences and brain activity and the degree of gastric distention.Method: 19 healthy males (age 22.2 +/- 2.5 y, BMI 21.8 +/- 1.5 kg/m(2)) participated in a randomized crossover study with two treatments: ingestion of a 500-kcal 150-mL liquid meal shake followed by a low (LV, 50 mL) or a high volume (HV, 350 mL) water load. At baseline and three times after ingestion satiety was scored, MRI scans were made to determine total gastric content volume (TGV) and functional MRI scans were made to measure cerebral blood flow (CBF).Results: TGV was significantly higher for HV compared to LV at all time points (p < 0.001) with relative differences between HV and LV of 292 +/- 37 mL after ingestion, 182 +/- 83 mL at t = 15 min and 62 +/- 57 mL at t = 35 min. Hunger decreased (p = 0.023) and fullness increased (p = 0.030) significantly more for HV compared to LV. Ingestion increased CBF in the inferior frontal gyrus and the anterior insula, but there were no differences between treatments. There were no significant correlations between appetite ratings and CBF values.Conclusion: Performing concurrent gastric MRI and CBF measurements can be used to investigate neural correlates of gastric distention. Increased distention did not induce significantly greater brain activation. Future research should further examine the role of the inferior frontal gyrus in satiety.