The molecular structures of several polypeptides isolated from hypothalamic tissue have been established and the synthesis of these compounds has been achieved. These polypeptides selectively stimulate or inhibit the release of anterior pituitary hormones and melanocyte-stimulating hormone. Various studies indicate their important physiological role and support the concept that some of these polypeptides are hormones. Some synthetic hypothalamic hormones and their derivatives may find important clinical and veterinary applications.