Ghrelin, a novel peptide modified by n-octanoic acid at the third serine residue (Ser(3)), serves as an endogenous ligand for the growth hormone secretagogue receptor (GHS-R) 1a. The octanoyl modification at Ser(3) is essential for receptor binding or growth hormone release. Here, we report the purification of caprine ghrelin and its physiological role in goats. The major form of caprine ghrelin is a 27 amino acid peptide that is octanoylated (C8:0) at Ser(3) and lacks Gln(14), which is present in rat and human ghrelin. Additionally, we identified various acyl modifications in caprine ghrelin: nonanoic (C9:0), decanoic (10:0), unsaturated octanoic acids (C8:1), and an unidentified fatty acid modification. We observed that differences in acyl modifications affected GHS-R1a activation. In addition, administration of synthetic bovine ghrelin increased plasma growth hormone (GH) levels in goats. Thus, the present study indicates a structural divergence in caprine ghrelin and suggests that ghrelin is involved in GH release in ruminants.