Extracts of rat atrial muscle lowered basal aldosterone release from rat adrenal glomerulosa cell suspensions, and partially inhibited the stimulation of aldosterone release by adrenocorticotropic hormone (ACTH) and angiotensin II. Atriopeptin I, an atrial peptide with natriuretic, diuretic and smooth muscle relaxant activities, significantly decreased basal aldosterone release at 1 pM concentrations. Also, atriopeptin I decreased the sensitivity of the glomerulosa cells to adrenocorticotropin and angiotensin II. These data suggest that peptides contained in mammalian atria affect sodium excretion not only by a direct effect on the kidney, but also indirectly through inhibition of aldosterone production.