The effects of intracerebroventricular (icv) administration of adrenomedullin (AM) on plasma oxytocin (OXT), c-Fos protein (Fos), and c-fos messenger RNA (mRNA) in the paraventricular (PVN) and supraoptic nuclei (SON) of the rat were investigated using RIA for OXT, immunohistochemistry for Fos, and in situ hybridization histochemistry for c-Fos mRNA. Central administration of AM caused a significant increase in the plasma OXT level. Intracerebroventricular administration of AM caused a marked induction of Fos-like immunoreactivity (LI) in the PVN and in the dorsal parts of the SON. In the PVN and SON, OXT-LI cells predominantly exhibited nuclear Fos-LI in comparison with arginine vasopressin-LI cells. In situ hybridization histochemistry revealed that the induction of c-fos mRNA in the PVN and SON was increased in a dose-related manner 30 min after icv administration of AM. This induction was reduced by pretreatment with the AM receptor antagonist, human AM-(22-52)-NH2. These results suggest that central AM is responsible for activating the neurosecretory cells in the PVN and SON via selective AM receptors, and that AM stimulates the secretion of OXT by activating hypothalamic OXT-producing cells.