The influence of gamma-hydroxybutyrate (GHB; 10, 50 or 100 mg/kg orally) and of its receptor antagonist, NCS-382 (25, 100 or 200 mg/kg orally, and 100 or 200 mg/kg intraperitoneally), on gastric emptying was studied in rats by measuring the serum level of acetaminophen (20 mg/rat orally, 30 min after GHB or NCS-382) 15, 30, 45 and 60 min after acetaminophen administration, or the amount of acetaminophen still present in the stomach 30 min after its administration. The highest dose of GHB produced a significant increase in 15 and 30 min serum levels of acetaminophen, indicating an acceleration of gastric emptying. A similar result was obtained with the prokinetic drug cisapride, at the oral dose of 2 mg/kg. On the other hand, NCS-382 significantly and dose-dependently reduced the serum levels of acetaminophen at every time of blood sampling, indicating a delay of gastric emptying, an effect confirmed by the amount of acetaminophen still present in the stomach 30 min after administration. Moreover, NCS-382 antagonized the prokinetic effect of GHB. These results may suggest for GHB (and/or possibly for its metabolites) a role in rat stomach motility.