Experimental data indicate that adrenomedullin (AM) interacts at various levels with the renin-angiotensin-aldosterone system and the hypothalamic-pituitary-adrenal axis, but data from humans are scant. We examined the effects of intermediate-dose, short-term AM infusion on angiotensin II- and adrenocorticotrophic hormone (ACTH)-mediated hormone and haemodynamic responses in healthy subjects. Seven normal volunteers (age 18-25 years) completed a placebo-controlled crossover study. Each subject was studied on day 4 of two periods of a low-salt diet (40 mmol of sodium and 80 mmol of potassium daily), receiving incremental infusions of angiotensin II in the morning and ACTH in the afternoon of each study day, on a background infusion of AM (4 pmol.min(-1).kg(-1)) or vehicle (hemaccel). Achieved plasma AM levels (23+/-6 pmol/l) and peak angiotensin II levels (160 pmol/l) were similar on the two experimental days. While the pressor action of angiotensin II was attenuated by AM (P<0.01) and noradrenaline levels rose (P<0.05), the aldosterone response was unaltered. During ACTH infusion, AM increased heart rate (P<0.01), plasma adrenaline (P<0.01) and plasma noradrenaline (P<0.05), and augmented the cortisol response (P<0.01), but was without effect on aldosterone levels and blood pressure. We conclude that the threshold for the effects of AM on aldosterone secretion in humans is set higher than for other biological responses to this hormone, namely blood pressure, heart rate, sympathetic activity and cortisol secretion, under these experimental conditions.