Atrial natriuretic peptide (ANP) has been shown to inhibit angiotensin II (Ang II)-induced steroidogenesis and vasoconstriction. To investigate the role of Ang II in the renal response to ANP, a synthetic ANP (0.1 micron/kg/min, 60 min) was infused for 1 h in eight subjects with or without pretreatment with an inhibitor of the converting enzyme, enalapril (20 mg, p.o.), or Ang II (10 ng/kg/min). ANP infusion alone caused increases in urinary volume, urinary sodium excretion, and glomerular filtration rate (GFR). However, enalapril treatment abolished these diuretic and natriuretic effects of ANP. In this group, GFR was decreased and no tubular effects, which was estimated by urinary excretion of sodium and phosphate, were observed. The anti-natriuretic effects of exogenous Ang II were reversed by concomitant ANP infusion, which inhibited both proximal and postproximal sodium reabsorption induced by Ang II without changing the GFR. These results indicate that endogenous Ang II plays an obligatory role in the natriuretic response to ANP and also suggested that ANP inhibits Ang II-stimulated tubular reabsorption of sodium.