Intermedin nucleic acid compositions and their encoded polypeptides and variants thereof are provided. Intermedin is a novel ligand for the calcitonin receptor-like receptor. In addition to its use as a therapeutic agent, intermedin sequences are utilized in screening and research methods for the determination of specific analogs, agonists, antagonists and mimetics. Intermedin is highly expressed in the intermediate lobe of the pituitary and is shown to stimulate prolactin release by anterior pituitary cells, and to release of growth hormone. Intermedin treatment leads to blood pressure reduction both in normal and hypertensive subjects, as well as the suppression of gastric emptying activity.