In essential hypertension (ESS) whole body and vascular nitric oxide (NO) synthesis is generally thought to be reduced. We therefore investigated the systemic and renal responses to acute treatment with NG-monomethyl-L-arginine (L-NMMA), a competitive NOS-inhibitor, in 12 patients with ESS and 18 healthy controls (CON) in a randomized, placebo-controlled study. Main effect parameters were renal hemodynamics (glomerular filtration rate [GFR] and renal plasma flow [RPF]), systemic blood pressure (BP), and fractional excretions of sodium (FENa) and lithium (FELi). Experiments were performed on two occasions for each subject studying the effects of either L-NMMA (3 mg/kg intravenously) or placebo. The patients with ESS were studied after at least 14 days off antihypertensive medication. Renal hemodynamics were assessed by the clearances of 125I-hippuran (RPF) and 51Cr-EDTA (GFR). The L-NMMA induced a significant increase in systemic BP and significant reductions in RPF, FENa, and FELi in both groups. The increase in diastolic BP was significantly attenuated in ESS (ESS: 8% ± 2% v CON: 14% ± 2%, P < .05). The GFR and RPF were equally reduced by L-NMMA in both groups (RPFESS: −19% ± 4% v RPFCON: −15% ± 3%, P = not significant [NS]). However, the reduction in FENa was enhanced in ESS (ESS: −42% ± 7% v CON: −25% ± 3%, P < .01). The FELi decreased equally in both groups (ESS: −17% ± 2% v CON: −17% ± 6%, P = NS). It is concluded that acute NO blockade in ESS is accompanied by a reduced systemic pressor response, an unchanged renal hemodynamic response, and an enhanced reduction in FENa. The results suggest that patients with essential hypertension are highly dependent on NO to maintain sodium excretion. Am J Hypertens 2007;20: 287-295 © 2007 American Journal of Hypertension, Ltd.