Amylin (also known as islet amyloid polypeptide and diabetes-associated peptide) has recently been shown by us to have a potent hypocalcemic effect in rat and rabbit owing to inhibition of osteoclast-mediated bone resorption. The hypocalcemic potency of amylin was found to be second only to that of calcitonin (CT) and is 100-fold more potent than calcitonin gene-related peptide. Here we demonstrate that amylin has a hypocalcemic effect in patients with Paget's disease of bone. Both human CT (hCT) and amylin induced a maximum hypocalcemic effect 2 h following intravenous administration of the peptides (p less than 0.001). Although on a molar basis amylin is less potent than CT, it exhibits a significantly prolonged hypocalcemic effect compared to hCT. Here we demonstrate for the first time a profound hypocalcemic effect of amylin in the human, despite sharing only 15% amino acid sequence identity with hCT.