The iv administration of L-arginine, a precursor of endothelium-derived relaxing factor/nitric oxide, is known to decrease blood pressure in humans by its direct vasodilatory effects. The purpose of the present study was to determine whether L-arginine infusion modifies the renin-angiotensin (Ang)-aldosterone system as well as blood pressure and renal hemodynamics. L-Arginine and saline vehicle were iv administered to 10 healthy male subjects in random order on different days. L-Arginine infusion (500 mg/kg over 30 min) decreased mean blood pressure (from 81.2 +/- 2.7 to 74.0 +/- 2.5 mm Hg; P < 0.001) and renal vascular resistance (from 0.085 +/- 0.007 to 0.074 +/- 0.006 mm Hg/mL.min; P < 0.01) and increased heart rate (from 60.3 +/- 2.7 to 69.7 +/- 2.1 beats/min; P < 0.001) and renal plasma flow (from 616.6 +/- 37.8 to 701.0 +/- 49.2 mL/min; P < 0.05). L-Arginine reduced serum Ang-converting enzyme activity (from 10.4 +/- 0.6 to 8.9 +/- 0.5 nmol/mL.min; P < 0.05) and plasma Ang-II (from 19.3 +/- 3.3 to 12.7 +/- 2.8 pg/mL; P < 0.001), but had no effect on PRA or the glomerular filtration rate. The saline vehicle did not alter any of these parameters. The iv administration of L-arginine (endothelium-derived relaxing factor/nitric oxide) may reduce the plasma Ang-II concentration by inhibiting Ang-converting enzyme. The mechanism by which L-arginine infusion decreases blood pressure can be at least in part explained by inhibition of the renin-Ang system.