Neuromedin S is a neuropeptide agonist of the neuromedin U (NMU) receptors that increases calcium concentrations in CHO cells overexpressing NMU1 and NMU2 (EC50s = 65 and 91 pM, respectively). Neuromedin S (1 nmol, i.c.v.) induces phase shifts in the circadian rhythm of locomotor activity in rats without altering the circadian period length. It also suppresses food and water intake in a dose-dependent manner when administered to rats during the dark period at doses ranging from 0.1 to 5 nmol. Co-administration of neuromedin S (1 nmol, i.c.v.) inhibits the ability of neuropeptide Y , ghrelin , and agouti-related protein (ARP) to stimulate food intake in rats by greater than 50%. Neuromedin S (0.2 nmol, i.c.v.) increases vasopressin levels in rat plasma within five minutes to levels five times greater than a saline control and decreases urinary volume by 25% during the dark period.