The teleost adrenomedullin (AM) family consists of three groups, AM1/AM4, AM2/AM3 and AM5. In the present study, we examined the effects of homologous AM1, AM2, and AM5 on drinking and renal function after peripheral or central administration in conscious fresh water eels. AM2 and AM5, but not AM1, exhibited dose-dependent (0.01-1 nmol/kg) dipsogenic and antidiuretic effects after intra-arterial bolus injection. The antidiuretic effect was significantly correlated with the degree of associated hypotension. To avoid the potential indirect osmoregulatory effects of AM-induced hypotension, infusion of AMs was also performed at non-depressor doses. Drinking was enhanced dose-dependently at 0.1-3 pmol/kg/min of AM2 and AM5, matching the potency and efficacy of angiotensin II (ANG II), the most potent dipsogenic hormone known thus far. AM2 and AM5 infusion also induced mild antidiuresis, while AM1 caused antinatriuresis. Additionally, AMs were injected into the third and fourth ventricles of conscious eels to assess their site of dipsogenic action. However, none of AMs at 0.05-0.5 nmol induced drinking, while ANG II was highly dipsogenic. AM2 and ANG II injected into the third ventricle increased arterial pressure, while AM5 decreased it in a dose-dependent manner, and both AM2 and AM5 decreased blood pressure when injected to fourth ventricle. These data suggest that ciculating AM2 and AM5 acts on a target site in the brain that lacks the blood-brain barrier. Collectively, the current study showed that AM2 and AM5 are potent osmoregulatory hormones in the eel and their actions imply involvement in seawater adaptation of this euryhaline species.