Aim: To evaluate the effect of single administrations of asimadoline, a kappa-opioid agonist, on satiation volume, postprandial symptoms and gastric volumes. Methods: Healthy subjects received oral placebo, or 0.5 or 1.5 mg asimadoline in a randomized, double-blind fashion 1 h prior to testing. We assessed effects on the volume of Ensure to achieve full satiation and postprandial symptoms 30 min after meal, and on gastric volume ( fasting and postprandial) measured by Tc-99m-single photon emission tomography ( SPECT) imaging. Results: Thirteen healthy subjects were studied in each treatment arm. Compared to placebo, asimadoline 0.5 mg decreased postprandial fullness ( P = 0.027) without affecting the volume ingested at full satiation P = 0.6). Asimadoline 1.5 mg decreased satiation during meal, allowing increased satiation volumes ( P = 0.008) and tended to decrease postprandial fullness ( P = 0.067), despite higher volumes ingested. There was a significant treatment - gender interaction in the effect of asimadoline on gastric volumes ( P < 0.05). Asimadoline 0.5 mg ( not 1.5 mg) increased fasting ( P = 0.047) and postprandial ( P = 0.009) gastric volumes in females but decreased fasting volumes in males ( P = 0.008). The effect of asimadoline on gastric volume did not explain the effect observed on satiation volume ( P = 0.371) or postprandial fullness ( P = 0.399). Conclusion: A single oral administration of asimadoline decreases satiation and postprandial fullness in humans independently of its effects on gastric volume.