The effect of adrenomedullin, a novel peptide of 52 amino acids, on vascular tone was investigated in the perfused rat mesenteric vascular bed. In the vasculature contracted with methoxamine, perfusion of adrenomedullin (10(-11)-10(-7) M) caused a concentration-dependent decrease in perfusion pressure due to vasodilation. Additionally, a bolus infusion of adrenomedullin (300 and 500 pmol) produced a long-lasting vasodilator response, which was not affected in the presence of atropine (10(-7) M) and propranolol (10(-7) M). However, this response was inhibited in the presence of CGRP [8-37] (10(-6) M), an antagonist for CGRP receptor. These results suggest that adrenomedullin induces nonadrenergic and noncholinergic vasodilation in which CGRP receptors may be involved.