Sustained and/or episodic hypotension during hemodialysis (HD) is an important clinical issue. Plasma adrenomedullin (AM) is increased in HD patients with sustained hypotension, but little is known about its implications for episodic hypotension. Ghrelin may also contribute to the pathophysiology of hypotension in HD patients. We evaluated plasma levels of AM and total ghrelin in sustained hypotensive (SH; n = 23), episodic hypotensive (EH; n = 30) and normotensive (NT; n = 23) HD patients. In the EH group, the relationship between low blood pressure during HD and circulating levels of AM and ghrelin was also evaluated. Plasma levels of AM were significantly higher in SH (34.3 +/- 8.3 fmol/ml, p<0.01) than in NT patients (27.6 +/- 5.2 fmol/ml), but not in EH patients (30.8 +/- 6.1 fmol/ml). There was no significant difference of plasma total ghrelin in SH (548.1 +/- 426.5 fmol/ml) and in EH patients (544.6 +/- 174.3 fmol/ml), compared with NT patients (400.0 +/- 219.7 fmol/ml). On the other hand, in EH patients, the "suppressed blood pressure ratio" during HD significantly correlated with plasma AM (r = 0.77, p<0.001) and with total ghrelin levels (r = 0.44, p<0.05). Our results suggest that ghrelin, as well as AM, may play an important role as vasodilator local hormones and regulation of blood pressure during HD, especially the occurrence of EH. Further studies are necessary to clarify the implication of these hormones in the control of hypotension during HD.