Background/Aims: The aim was to determine whether genetic selection of sheep for body composition could be accounted for by changes in the level of expression of genes for appetite-regulating peptides in the hypothalamus. We examined gene expression in the hypothalamus of genetically lean, normal and fat ewes (n = 5/group). Methods: Plasma growth hormone (GH) and metabolic indicators were measured and gene expression in brains was quantified by in situ hybridization. Results: Body weight and voluntary food intake (VFI) were similar between groups, but lean and fat animals respectively had low and high indices of adiposity. GH levels were higher in lean and fat animals than in controls. In the arcuate nucleus (ARC), neuropeptide Y (NPY) expression/cell was higher in the lean animals than in normal animals, but overall NPY expression was similar in fat and normal animals. Pro-opiomelanocortin (POMC) and leptin receptor (ObRb) expression in the ARC was similar across groups. Orexin (ORX) and melanin-concentrating hormone (MCH) expression was inversely correlated to adiposity, being higher in lean and lower in fat animals. Conclusion: Expression of genes for orexigenic neuropeptides is altered in a consistent way. Energy expenditure is reduced by MCH but increased by ORX, so increased expression of the latter may cause increased energy expenditure in the lean animals and vice versa in the fat animals.