There is now much evidence that atrial natriuretic peptide (ANP) is important in the control of sodium balance. There is also evidence that ANP interacts with the renin-angiotensin system at several levels. In this study we investigated a further possible interaction between ANP and angiotensin II (ANG II) in the control of renal water and electrolyte excretion. In normal male volunteers, ANP caused urinary sodium excretion to rise significantly from baseline (+80 +/- 44 mumol/min) whereas ANG II was potently antinatriuretic (-125 +/- 36 mumol/min). When ANP was administered against a nonpressor background infusion of ANG II, urinary sodium excretion rose from a new lower level (-93 +/- 22 mumol/min) to a rate not significantly different from control (-22 +/- 25 mumol/min). In contrast to that of sodium, potassium excretion and urinary volume remained significantly below baseline levels when ANP was administered against a background infusion of ANG II. These results suggest that ANP and ANG II interact within the kidney in the control of water and electrolyte excretion.