We investigated the relationship between microalbuminuria (an indicator of systemic and renal endothelial dysfunction), inflammation (high-sensitivity C-reactive protein [CRP]) and endothelial function (hemodynamic response to acetylcholine [ACh] in the forearm) in 110 never-treated subjects with uncomplicated essential hypertension and serum creatinine within the normal range. Microalbuminuria was associated with the hemodynamic response to ACh (r=0.27, p=0.006) and with serum creatinine (r=0.34, p<0.001), and these associations held true in multivariate analyses. On the other hand, microalbuminuria was largely independent of serum CRP. Since microalbuminuria, response to ACh and serum CRP are all considered risk factors for renal insufficiency and since these factors were significantly related to creatinine at univariate analysis, we tested their association with creatinine in a multiple regression model including also the full set of Framingham risk factors. In this analysis, serum CRP and microalbuminuria maintained a significant association with serum creatinine, while the hemodynamic response to ACh lost substantial predictive value for serum creatinine. In conclusion, microalbuminuria in essential hypertension is weakly related to the vasodilatory response to ACh and unrelated to inflammation but maintains an independent link with serum creatinine. Collectively, these associations suggest that microalbuminuria reflects a local (renal) endothelial dysfunction and that it may contribute to renal impairment independently of inflammation and hemodynamic endothelial dysfunction in hypertensive patients.