To investigate the effects of a small rise in the plasma atrial natriuretic peptide (ANP) concentration, 6 normal subjects received 2-h low dose (2 pmol/kg·min) infusions of both 28 [human αhANP-(99–126)]- and 26 [human ANP-(101–126)] -amino acid peptides in a placebo-controlled study. Both peptides induced more than 2-fold increases in urinary sodium, calcium, and magnesium excretion. Effective renal plasma flow was slightly reduced, glomerular filtration rate did not change, and renal filtration fraction increased during the ANP infusions. Plasma renin, angiotensin II, and aldosterone concentrations fell by about 50%. Arterial blood pressure and plasma catecholamines did not change. Hematocrit and serum albumin concentrations rose significantly. ANP effects on urinary electrolytes and the renin-angiotensin-aldosterone system were sustained for over an hour after completion of the ANP infusions. The two peptides did not differ in their effects. These results are consistent with a physiological role for plasma ANP in the regulation of extracellular fluid volume and demonstrate that minor N-terminal truncation of ahANP has little effect on its biological activity.