The aim of this study is to evaluate the medium term treatment effects of the beta-blocker nebivolol on the endogenous anti-hypertensive and anti-inflammatory agent Atrial Natriuretic Peptide (ANP) plasma levels in patients with moderate uncomplicated essential hypertension. The drug was given orally for 30 days to 25 patients. The daily dose was 5 mg once every morning. Quantitative determination of ANP was made by Radioimmunoassay (RIA). At the end of this clinical trial, plasma ANP levels showed a statistically non significant tendency to increase by 10.99% while both systolic (SBP) and diastolic (DBP) blood pressure as well as the diameters ofthe left cardiac cavities showed a statistically significant decrease. What was interesting was the fact that there was a statistically significant increase of 44.7% in the ratio ANP/SBP following the reduction of arterial blood pressure. This increase was the most important and essential finding as it indicated a real increase of ANP plasma levels. This result was obtained even though pressure and afterload, the homologous mechanical stimulatory parameters for ANP secretion, of the left cavities were diminished. These findings provide strong indications which were supported by several previous trials, that the increase in plasma ANP following the administration of beta-adrenergic blockers to hypertensive patients was a primary effect of beta blockade and not a mechanical one secondary to a negative inotropic action on the left ventricle. This primary action contributed to the anti-hypertensive effect of nebivolol during this trial.It is known that the short-term effect of antihypertensive drugs is due to their action on cardiac output and/or peripheral resistance. However, their long-term effect is due to changes in the pressure/natriuresis relationship. No conventional hemodynamic effect can provide a satisfactory explanation for the chronic long-term antihypertensive efficacy of p-adrenergic blockers.Thus, it is quite reasonable to try to explain the effects of the above drugs on the arterial pressure by evaluating their action on factors that control pressure-natriuresis. Such a factor is Atrial Natriuretic Peptide (ANP) which also possesses antiinflammatory properties (1). Furthermore, the links between inflammation and cardiovascular diseases, especially hypertension, are well documented (2).