Ghrelin is a recently identified orexigenic hormone secreted by the stomach and has been implicated in meal-time hunger. Several experiments demonstrate a transient surge in ghrelin secretion shortly before a scheduled meal, suggesting from the involvement of cephalic mechanisms. If ghrelin secretion is stimulated by hunger in sheep, plasma levels of ghrelin should be modified by different feeding regimens that affect hunger drive. To test this hypothesis, we investigated changes in plasma ghrelin concentrations in fed Suffolk rams ad libitum and in rams either twice or four times daily. Plasma ghrelin levels increased (P < 0.05) abruptly just before every feeding period in sheep fed twice and four times daily and then fell shortly after feeding. Peak levels of the pre-prandial ghrelin surge were higher (P < 0.01) in animals fed twice daily than in animals fed four times daily, leading to greater (P < 0.05) areas under response curves over 12 h. In contrast, the plasma ghrelin levels remained relatively low and constant in sheep fed ad libitum, with no evidence of surges in plasma ghrelin levels. These results confirm that the transient surge in plasma ghrelin levels occurs just before feeding and demonstrate that this can be modified by the feeding regimen in sheep. (C) 2002 Elsevier Science (USA). All rights reserved.