Adrenomedullin (AM) is a vasodilatory peptide hormone, playing a key role in the regulation of cardiovascular homeostasis. In view of the circulatory failure in sepsis, it is still debated as to whether the occurrence of vascular hyporeactivity against AM plays a causative or protective role. This study was designed as a prospective, controlled trial to elucidate the hemodynamic response following a titrating infusion of human AM in healthy and endotoxemic sheep. ANOVA demonstrated that AM infusion produced hypotension and tachycardia, and increased cardiac index in a dose-dependent manner, both in healthy and endotoxemic sheep. In addition, AM application reduced pulmonary vascular resistance index in ovine endotoxemia (P = 0.02). These findings confirm that AM produces a hyperdynamic circulation, in the presence and absence of systemic inflammation. Further, exogenous AM could possibly be a useful adjunct in the common setting of sepsis-associated pulmonary hypertension. (C) 2002 Elsevier Science (USA). All rights reserved.