Circulating endothelial progenitor cells (EPCs) promote vascular reparative processes and their concentration has been inversely correlated with the endothelial condition and cardiovascular risk. This impaired angiogenic function has been found in patients with chronic renal failure, partially justifying the accelerated atherosclerosis pattern they show. We analyzed the 'in vitro' effect of the addition of uremic solutes - p-cresol, homocysteine, urea and creatinine - to the culture medium on EPCs concentration, proliferation and adhesion and compared with the proliferation on control medium in a time and concentration-dependent manner. We also analyzed the relationship between clinical and biochemical atherosclerosis risk parameters (creatinine, urea, cholesterol, HDL, LDL, proteinuria, GFR, homocysteine and fibrinogen) and EPCs concentration in 94 renal transplant patients (RT) and in 39 controls. On the other hand we compared the EPCs proliferative capacity between 70 RT and 30 controls. Study subjects were between 25-75y. and GFR was above 15 mL/min in RT and 60 mL/min in controls. All RT were either on cyclosporine (n=43) or tacrolimus (n=51). Fifty. were also under MMF. Only 34 RT were on steroids. EPCs proliferation and adhesion was progressively impaired in presence of growing concentrations of uremic solutes. EPCs concentration and proliferation was significantly impaired in RT compared to controls in the univariate analysis. In the regression multiple analysis, EPCs concentration correlated directly with HDL, GFR and body weight, and inversely with LDL and fibrinogen, both in RT and C (r2=0.26, p<0.001). HDL, LDL, body weight and RT were independent predictors of EPCs proliferation (r2=0.172, p<0.001). EPCs proliferation and adhesion was also impaired in presence of uremic solutes. Concentration of EPCs was higher in RT taking MMF compared to those non receiving MMF (51.6±37 vs. 36.8±32, p=0.01). In contrast, EPCs proliferation was reduced in RT on MMF (353.7±217.7 vs. 395.3±243.9, p=0.454). Corticosteroids did not influence the concentration and proliferation of EPCs. Isolated uremic solutes reduced EPCs proliferation and adhesion in a concentration-dependent manner. EPCs concentration correlates directly with HDL, GFR and body weight, and inversely with LDL and fibrinogen. HDL, body weight and RT are independent predictors of EPCs proliferation. Our study suggests that the deleterious effect of uremic solutes in the endothelium starts in the first endothelial line. Impaired renal function may be a potent inhibitor factor of the cardiovascular repair mechanisms in RT patients by means of the reduction of EPCs concentration, proliferation, differentiation and adhesion. Immunosuppression may have an additional deleterious effect in EPCs proliferation.