Endothelium plays a primary role in local regulation of vascular activity by synthesis and release of vasoactive substances, including the endothelium-derived relaxing Ž. factor, now identified with nitric oxide NO, a labile substance derived from L-arginine. From its discovery wx 1, 2, NO has been recognized as a major intercellular, and wx perhaps intracellular, mediator 1, 2. NO has potent biological properties as a vasoactive, platelet-regulatory, neurowx transmitter and also cytotoxic agent 3. Disorders of the endothelial NO synthase pathway might play a role in cardiovascular disorders including systemic and pulmonary wx wx hypertension 4–8, hypercholesterolaemia 9 and atherow x sclerosis 10, 11 although it is still unclear whether the decrease in endothelium-dependent vasorelaxation observed in hyperlipidaemia results from an increase in NO w x inactivation 12, 13 or a decreased formation of this comw x pound 14, 15. Investigators used arginine, the substrate of NO synthase, and antagonists of NO synthase as pharmacological means to manipulate the pathway. Only recently the idea emerged that arginine is not only a substrate for the enzyme which converts it to NO and citrulline but also a nutrient whose intake is highly variable among individuals and among populations. Although arginine was recently presented as a new possible pharmacological agent for wx atherosclerosis 16, the hypothesis that chronic high or low intake of arginine may play a role in coronary heart Ž. disease CHD has not been documented yet. In the present issue of CardioÕascular Research, Bode-Boger et al. report that dietary arginine interferes with the metabolism of eicosanoids in a rabbit model of hyperwx cholesterolaemia 17. The cholesterol-induced increase of