Alcohol has been reported to have appetite-stimulating properties in humans. The underlying mechanism is unknown. Gastrointestinal hormones, such as ghrelin and peptide YY (PYY), could be involved as mediators of the alcohol effect because ghrelin stimulates the appetite and PYY appears to induce satiety. This investigation was undertaken with the intention to study that issue. Twelve young and healthy volunteers of both sexes participated in 2 experiments (experiments A and B), which were performed in random order 1 week apart. Alcohol (0.55 g ethanol per kilogram) was ingested in experiment A, drinking water in experiment B. Venous blood samples were collected before and repeatedly after the drinks. Serum concentrations of total ghrelin, octanoylated ghrelin (the bioactive form of the hormone), PYY, and ethanol were determined over a period of 5 hours. In experiment A, the ethanol level increased from 0 to 12.5 +/- 0.7 mmol/L in 1 hour (P < .001), and then began to decrease. In experiment B, the ethanol level remained at zero throughout the entire experiment. Alcohol induced significant declines in total and octanoylated ghrelin concentrations from 30 minutes on. The total ghrelin level reached its lowest point 5 hours after the alcohol intake (36% +/- 4% below the basal level; P < .001). The octanoylated ghrelin level fell 48% +/- 5% below the basal level in 2 hours (P < .001) and then tended to level out. Drinking water left both total and octanoylated ghrelin levels unaffected. The PYY level remained unchanged after both alcohol and water ingestion. Alcohol has a strong inhibitory influence on human ghrelin secretion, but has no effect on circulating PYY levels. This makes it unlikely that the orexigenic effect of alcohol is mediated by either of these 2 hormones.