Background Atherosclerosis may be manifested as an endothelial dysfunction with a concurrent reduced bioavailability of nitric oxide (NO). Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of NO synthase that can modulate NO production and thereby affect endothelial function. ADMA has been observed to associate with several cardiovascular risk factors and it may be a circulating marker of endothelial dysfunction and thus subclinical atherosclerosis. However, the role of ADMA in the development of vascular disease is still largely unclear. Objectives To study how plasma ADMA is related to early atherosclerotic changes like carotid intima-media thickness (IMT), indices of vascular function, and atherosclerosis risk factors. Furthermore, the association of dietary factors with ADMA and the effect of statin therapy on plasma concentration of ADMA were studied. Subjects and Methods The study was based on five separate study populations (studies I-V), consisting of 373 patients or controls. In study I, there were forty-seven healthy controls, 16 men with borderline hypertension and 14 men with heterozygous familial hypercholesterolemia. This study evaluated the association between plasma ADMA and myocardial blood flow measured by positron emission tomography (PET) as well as carotid IMT measured by ultrasound. Study II included eighty-six type 2 diabetic patients and 65 controls with a comparable distribution of age and gender. In this study, plasma levels of ADMA were compared between subjects with type 2 diabetes and non-diabetic controls and plasma ADMA concentrations were related to glycemic control and glomerular filtration rate (GFR). In study III, forty-four mild to moderately hypercholesterolemic subjects (29 men and 15 women), participated in a randomised, double-blind, placebo-controlled trial to determine the effect of high dose atorva- or simvastatin therapy on plasma arginine derivatives. Thirty-four subjects (14 men and 20 women) participated in study IV to determine the impact of dietary factors and alcohol consumption on the plasma concentrations of arginine derivatives. In that study, seven-day food records were used to analyze diet and alcohol intake. Study V evaluated, in sixty-seven men, how plasma ADMA relates to blood pressure and other non-invasively studied indices of hemodynamics. Results There was a significant direct association between plasma ADMA and carotid IMT as well as an inverse association to the reduced dipyridamole induced vasodilatory function in young men as measured by PET (study I). In this study, borderline hypertensive subjects not on antihypertensive treatment had higher plasma ADMA levels than controls. In study II, type 2 diabetic subjects had significantly lower plasma ADMA levels compared to controls, possibly due to increased kidney GFR. There was no significant correlation between plasma ADMA and blood pressure in studies IV and V or other measured indices of hemodynamics (study V). In study V, subjects on antihypertensive treatment had lower plasma ADMA levels than non-treated subjects. There were no significant association between plasma ADMA and risk factors of atherosclerosis such as hypercholesterolemia or smoking in any of the studies. In study III, high dose simvastatin and atorvastatin treatment effectively decreased plasma total and LDL cholesterol but had no influence on plasma ADMA concentration. In dietary study IV, high amounts of energy derived from carbohydrates were significantly associated with low plasma ADMA levels and ADMA concentration was significantly higher in alcohol drinkers than in abstainers. Conclusions Plasma ADMA was associated with early atherosclerotic changes like carotid IMT and hyperemic myocardial blood flow measured by PET but not with risk factors of atherosclerosis. High amounts of energy received from carbohydrates were strongly associated with low plasma ADMA concentrations but statin treatment had no influence on plasma ADMA.