Aprepitant, an NK1 receptor antagonist, is approved for the treatment of chemotherapy-induced or postoperative emesis by blocking NK1 receptors in the brain stem vomiting center. Effects of NK1 receptors on gastric functions and postprandial symptoms in humans are unclear; a single, crossover study did not show a significant effect of aprepitant on gastrointestinal transit. Our aim was to compare, in a randomized, double-blind, placebo-controlled, parallel-group study (12 healthy volunteers per group), effects of aprepitant vs. placebo on gastric emptying (GE) of solids (by scintigraphy) with a 320kcal meal, gastric volumes (GV, fasting and accommodation by SPECT), satiation (maximum tolerated volume, MTV) and symptoms after a dyspeptogenic meal of Ensure®. Aprepitant (125mg on day 1, followed by 80mg on days 2-5) or placebo, one tablet daily, was administered for 5 consecutive days. Statistical analysis was by unpaired rank sum test, adjusted for gender and BMI. To assess treatment effects on symptoms, we incorporated MTV in the model. Aprepitant increased fasting, postprandial and accommodation GV, and tended to increase volume to fullness and MTV by ~200kcal. However, aprepitant increased aggregate symptom, nausea and pain scores after ingesting the MTV of Ensure®. There was no significant effect of aprepitant on GE T1/2 of solids. We conclude that NK1 receptors are involved in the control of GV and in determining postprandial satiation and symptoms. Further studies of the pharmacodynamics and therapeutic role of NK1 receptor antagonists in patients with gastroparesis and dyspepsia are warranted.