The hypotensive peptide, adrenomedullin (AM), was first isolated from the tissue of human pheochromocytoma. Recently, AM-immunoreactivities have been found in the central nervous system, including the supraoptic and the paraventricular nuclei. In this study, the effect of centrally administered AM on arginine vasopressin (AVP) release was investigated in conscious rats. Intracerebroventricular injection of AM (1.0 microgram/rat) partially but significantly attenuated the plasma AVP increase induced by hyperosmolality (intraperitoneal (i.p.) injection of hypertonic saline (600 mosmol/kg)) at 30 min after the injection. It also significantly attenuated the plasma AVP increase induced by hypovolemia (i.p. injection of polyethylene glycol) at 30 min after the injection. These results suggest that central AM might play an inhibitory role in both osmo- and baro-regulation of plasma AVP.