Objective: Increased arterial stiffness (AS) is an independent risk factor for cardiovascular disease. Endothelial nitric oxide (NO) is vasoprotective by decreasing not only vascular tone in resistance arteries, but also stiffness in conductance arteries. Asymmetric (ADMA) and symmetric (SDMA) dimethylarginines, endogenous inhibitors of NO synthesis from the precursor L-arginine (ARN), increase in conditions of oxidative stress and contribute to progression of endothelial dysfunction and arteriosclerosis. In essential hypertensives (EH) we investigated the relationship between systemic AS, as assessed by the ratio of pulse pressure (PP) to stroke volume (SV), with circulating levels of ADMA, SDMA, ARN and the activity of the renin-aldosterone system in resting conditions. Design and method: In 25 untreated grade I-II EH (age 50 ± 12 yrs, range 19–71, M/F = 15/10) blood pressure (BP, sphygmomanometer), heart rate (HR, EKG), stroke volume (SV, impedance cardiography) were measured after supine rest; venous blood was simultaneously sampled for plasma ADMA, SDMA, ARN (by HPLC), plasma renin activity (PRA) and aldosterone (Aldo)(by RIA). Results: Table shows means ± sd:Supine BP was 142/96 ± 15/8.4 mmHg, HR = 70.0 ± 9.5 bt/min; PRA was 0.3 ± 0.05 ng/ml/h (range 0.1–0.9) and Aldo 9.8 ± 0.7 ng/dl (range 3.7–17). AS (range 0.89–2.21 mmHg/ml) was directly related to age (r = 0.61, p < 0.05), to SDMA (r = 0.83, p < 0.01) and inversely to ARN/ADMA ratio, an indicator of NO production (r = -0.64, p < 0.05); AS was not related to PRA or Aldo. In a multiple regression analysis, SDMA was the best predictor of AS (p < 0.05). Conclusions: Systemic AS in EH was directly related to circulating levels of endogenous inhibitors of NO production. These data are compatible with an impaired activity of endothelial NO associated with increased stiffness of conductance arteries, a condition at higher cardiovascular risk in uncomplicated hypertensives.