Growth hormone (GH) secretagogues (GHSs) are small synthetic molecules that act through a specific G-protein-coupled receptor (GPCR) called GHS-R. Until the recent identification of ‘ghrelin' from rat and human stomachs, GHS-R was an orphan receptor (i.e. had no known natural ligand). Ghrelin is a 28-amino acid peptide with an essential n-octanoyl modification at Ser3. This peptide is found in the secretory granules of X/A-like cells, whose hormonal products and physiological functions have not been previously clarified. The discovery of ghrelin indicates that the release of GH from the pituitary might be regulated not only by hypothalamic GH-releasing hormone, but also by ghrelin derived from the stomach and hypothalamus.