Gastric first-pass metabolism of ethanol is an important determinant of blood alcohol concentrations. We studied five healthy volunteers after ingestion of ethanol (0.3 g/kg of body weight) and found that blood alcohol concentrations in the fed state (ie, 1 hour after a standard breakfast) were significantly higher when the subjects received 1 g of aspirin 1 hour before ingestion of ethanol than without the drug. In vitro, aspirin clearly decreased the activity of gastric alcohol dehydrogenase in human subjects and in rat models, but not that of hepatic alcohol dehydrogenase in rats. Furthermore, blood alcohol concentrations in rats were unaffected by ingestion of aspirin when ethanol was infused intravenously. Thus, aspirin may increase the bioavailability of ingested ethanol in humans, possibly by reducing ethanol oxidation by gastric alcohol dehydrogenase.