Human adrenomedullin (hADM) is a newly isolated peptide with hypotensive activity in normotensive rats. The objective of this study was to investigate the effect of hADM(13-52) on hypertensive animals. hADM(13-52) induced a dose-dependent decrease in the blood pressure of spontaneously hypertensive rats and renal hypertensive rats. This result suggests that hADM is a novel antihypertensive peptide. In isolated rat aortic arteries, hADM(13-52) produced nitric oxide dependent relaxation and inhibited endothelin 1 and angiotensin II release. These in vitro effects may represent the molecular mechanisms underlying the hypotensive action of hADM in vivo.