Introduction: Nitric oxide (NO) plays an important role in the regulation of the cardiovascular system. It is produced by endothelial nitric oxide synthase (eNOS), which exhibits genetic polymorphisms. Although the clinically relevant polymorphism T-786 C reduces eNOS-promoter activity, it is not clear whether circulating nitrite/nitrate (NOx) are affected by this polymorphism. Materials and Methods: We addressed this issue by studying a homogeneous group of 200 healthy subjects (mates, Caucasians, nonsmokers, 18-56 years of age, and not taking any medication). Genotypes were determined by restriction fragment length polymorphism and circulating NOx were determined by chemiluminescence. Results: We found nonsignificant effects of the T-786C potymorphism on circulating NOx (mean +/- S.D.=52.2 +/- 21.4, 49.0 +/- 17.8, and 45.9 +/- 16.8 mu mol/L for genotypes "TT", "TC", "CC", respectively) and on total plasma cholesterol concentrations (both P>.05). No correlation was found between circulating NOx, and total plasma cholesterol concentrations (P>.05). Conclusions: Our study provides strong evidence that the T-786C potymorphism does not affect plasma NOx concentrations, which are believed to reflect endogenous production of NO. Therefore, our results suggest that this polymorphism does not affect endogenous NO production. (C) 2004 Elsevier Ltd. All rights reserved.1155375379