1. Adrenomedullin, a recently discovered 52-amino-acid peptide hormone, circulates in plasma at low picomolar levels in man. Animal studies and studies in vitro indicate that it has diverse biological actions, including vasodilatation, natriuresis and diuresis, and positive inotropism as well as anti-proliferative effects. We investigated the bioactivity of two doses of adrenomedullin in healthy human subjects. 2. Human adrenomedullin was given intravenously to eight male subjects at 2 and 8 ng min-1 kg-1, and haemodynamic, hormonal, renal and biochemical responses were recorded in a placebo (vehicle)-controlled, randomized study. 3. Compared with vehicle, adrenomedullin reduced mean arterial pressure (P = 0.05 for duration of infusion, mean difference at end of infusion 7.7 mmHg), systolic arterial pressure (P = 0.04 for duration of infusion, mean difference at end of infusion 10.7 mmHg) and at the lower dose reduced diastolic arterial pressure (P = 0.05 for lower dose, mean difference at end of infusion 6.3 mmHg) in the absence of compensatory responses in sympathetic activity or renin release. Urine volume and electrolyte excretion were unaffected. 4. The threshold for biological activity of adrenomedullin in man is lower, for arterial pressure than for renal or hormonal responses, and is evident at plasma concentrations seen in disorders of the circulation. Adrenomedullin may be an important hormone under pathophysiological circumstances.