Melatonin secretion is modulated by the light-dark schedule, mainly through a sympathetic input to the pineal gland. Besides this, arginine vasopressin (AVP) has been found in the pineal glands of several animal species and there is experimental evidence that AVP modulates melatonin secretion in animals. However, the interaction between vasopressin and melatonin secretion in humans has not been systematically investigated. We proposed to study the nocturnal melatonin pattern in patients with central diabetes insipidus (CDI) who lack endogenous secretion of AVP, and the effect on their melatonin secretion of the agonist for V2 type receptors: desmopressin (1-Desamino [8-D Arginine] vasopressin). Plasma melatonin levels were measured in 14 patients with CDI, every 2 h starting from 22:00 h until 06:00 h, following iv injection of saline (day 1) and 3 microg desmopressin (day 2) at 20:00 h. The lights were turned off at 22:30 h and the samples were taken in a dim light. The plasma melatonin secretion pattern was normal in patients with CDI. Desmopressin at a dose 3 times higher than the antidiuretic one did not modify the melatonin levels or the time of the peak secretion. In conclusion melatonin secretion is not modulated by AVP in humans.