Ghrelin is an endogenous ligand for the growth hormone secretagogue receptor that is synthesized predominantly in the stomach. Previous studies demonstrated that ghrelin stimulates growth hormone release and food intake. These data suggested that antagonism of ghrelin could serve as a useful treatment for eating disorders and obesity. To study the role of endogenous ghrelin in feeding performance further, we generated ghrelin-deficient (ghrl(-/-)) mice. Unexpectedly, ghrl(-/-) mice exhibited normal growth, cumulative food intake, reproduction, histological characters, and serum parameters. There were no differences in feeding patterns between ghrl(+/+) and ghrl(-/-) mice. Ghrl(-/-) mice displayed normal responses to scheduled feedings as seen for ghrl(+/+) mice. Memory-related feeding performances of ghrl(-/-) mice were indistinguishable from ghrl(+/+) littermates. These data indicate that ghrelin is not critical for feeding performance.