To investigate the mechanisms by which small changes in plasma levels of atrial natriuretic hormone (ANH) affect aldosterone, 10 normal young men were infused for 2 h with 0.6 pmol/kg.min human [Ser,Tyr28]ANH under 3 study conditions: 1) high salt diet (H), 2) low salt diet (L), and 3) low salt diet plus pretreatment with the angiotensin-converting enzyme inhibitor enalapril (LE). Baseline ANH levels were higher on H than on L or LE. A postural drop in ANH was observed when subjects went from standing to sitting. Plasma ANH levels increased during infusion by up to 4.5 pmol/L (H, 7.0 +/- 1.3 to 11.5 +/- 1.4; L, 4.3 +/- 0.6 to 8.7 +/- 1.1; LE, 4.2 +/- 0.5 to 8.6 +/- 1.5). At all time points, plasma ANH was well within the normal range. Plasma aldosterone did not change during H, decreased by about 60% for both low salt conditions, and remained suppressed at 1 h of recovery for L, but not for LE. This suggests that ANH can suppress aldosterone by both indirect and direct mechanisms, although the indirect mechanism appears to predominate. A prompt increase in urine flow was seen during ANH infusion and was sustained at 1 h of recovery, but little change was seen in urinary sodium or potassium excretion, heart rate, or blood pressure. The difference between the natriuretic and diuretic effects of ANH was seen under all conditions. These results support the hypothesis that within the normal physiological range, ANH is a regulator of salt and water metabolism in normal man.