Our aim was to validate the hypothesis that indices of early atherosclerosis and blood count of endothelial progenitor cells may be linked to abnormal plasma levels of an endogenous inhibitor of nitric oxide synthesis, asymmetric NG,NG-dimethyl-L-arginine (ADMA) in rheumatoid arthritis (RA). The results suggest that: 1. Plasma levels of ADMA are elevated in RA patients without cardiovascular disease or traditional risk factors. 2. The degree of EPC depletion in blood of RA patients is parallel to the magnitude of excessive ADMA accumulation. 3. In RA blood EPC depletion and elevated plasma ADMA/L-arginine ratio are independently related to carotid intima-media complex thickness, an index of early atherosclerosis. These abnormalities are also associated with the presence of carotid plaques in RA patients. 4. The imbalance between the substrate (L-arginine) and endogenous inhibitor of nitric oxide synthesis (ADMA) may contribute to accelerated atherogenesis in RA, which can partially be due to impaired mobilization of EPC from the bone marrow, a nitric oxide-dependent process.