Distension and chemosensitization of the stomach are insufficient to induce a ghrelin response, suggesting that postgastric feedback is required. This postgastric feedback may be regulated through insulin. We investigated the relation between gastric emptying rate and the postprandial ghrelin response as well as the role of insulin and other hormones possibly mediating this response. Fifteen healthy men [BMI 21.6 kg/m2 (SD 1.9), age 20.5 yr (SD 2.5)] were studied in a single-blind, crossover design. Subjects received two treatments separated by 1 wk: 1) a dairy breakfast in combination with a 3-h intravenous infusion of glucagon-like peptide-1 (GLP-1), which delays gastric emptying, and 2) a dairy breakfast in combination with a 3-h intravenous infusion of saline. Blood samples were drawn before breakfast and during the infusion. Postprandial ghrelin (total) responses were lower following the saline infusion compared with the GLP-1 infusion (P < 0.05). Acetaminophen concentrations, an indirect measurement of gastric emptying rate, were inversely correlated with total ghrelin concentrations (saline r = -0.76; 95% CI = -0.90, -0.49, GLP-1 r = -0.47; 95% CI = -0.76, -0.04). Ghrelin concentrations were only weakly correlated with insulin concentrations (saline r = -0.36; 95% CI = -0.69, 0.09; GLP- 1 r = -0.42; 95% CI = -0.73, 0.03), but strongly inversely correlated with GIP concentrations (saline r = -0.74; 95% CI= -0.89, -0.45; GLP-1 r = -0.63; 95% CI = -0.84, -0.27). In conclusion, our results support the hypothesis that ghrelin requires postgastric feedback, which may not be regulated through insulin. Conversely, our data suggest a role of glucose-dependent insulinotropic polypeptide in ghrelin secretion. Copyright © 2006 the American Physiological Society.