Adrenomedullin, a novel hypotensive peptide, was discovered in human pheochromocytoma. Although adrenomedullin exists also in normal adrenal medulla and several other organs, its effect on steroidogenesis in adrenal cortex has not been studied. We examined the effect of adrenomedullin on aldosterone secretion by the dispersed rat adrenal zona glomerulosa cells. Adrenomedullin (10(-12)-10(-7) M) did not affect basal aldosterone secretion. Adrenomedullin dose dependently inhibited aldosterone secretion stimulated by 10(-9) M angiotensin II and 10 mM potassium, whereas 10(-9) M ACTH-stimulated aldosterone was not significantly inhibited by adrenomedullin. N6,O2'-dibutyryladenosine 3':5'-cyclic monophosphate (db-cAMP, 10(-5)-10(-3) M) and Ca+ ionophore A23187 (10(-8)-10(-6) M) stimulated aldosterone secretion dose dependently, and A23187-stimulated secretion was significantly inhibited by adrenomedullin (10(-8) M), but db-cAMP-stimulated secretion was not inhibited by adrenomedullin. Our data suggest the possibility that adrenomedullin is a novel inhibitory peptide of aldosterone secretion induced by increasing concentration of intracellular free calcium.