In this study, the aim is to observe the renin-angiotensin system (RAS) and endothelium after phlebotomy in healthy blood donors. Healthy blood donors were divided into two subgroups according to the presence of hypertensive relatives (Group 1) or not (Group 2). Plasma levels of renin, nitric oxide (NO) and plasminogen activator inhibitor 1 (PAI-1) were studied before and after phlebotomy in each group. 400-500 mL of blood was taken in phlebotomies as usual. NO levels were studied by chemoluminescence method, PAI-1 activity were studied bye chromogenic assay method and plasma renin activity were studied by enzymatic kinetic methods. No statistically significant difference was observed between the mean baseline plasma renin, NO and PAI-1 level of the two groups. Evident increase was observed in the (stimulated) mean plasma levels of PRA, PAI-1 activity and NO levels after phlebotomy (p<0,001). The increase in mean plasma levels of PRA and PAI-1 activity is more evident in group 1 than group 2 after phlebotomy. Although mean plasma NO levels increased in both groups after phlebotomy, increase in group 1 was less than that in group 2. As a conclusion, increased renin, NO and PAI-1 response after phlebotomy in normotensive subjects with or without a family history of hypertension suggests the presence of abnormal RAS and endothelial function in the early stages of hypertension.