BACKGROUND: We evaluated the effect of the point mutation of guanine to thymine at nucleotide position 894 (G894T) of the endothelial nitric oxide synthase (eNOS) gene on inflammatory and oxidative stress markers. METHODS: We studied genetic information from 270 men (18-87 years old) and 325 women (18-89 years old). Participants without any clinical evidence of cardiovascular or other atherosclerotic disease were randomly selected from the general population according to the age-sex distribution of Athens greater area. Genomic DNA was extracted from 2 to 5 mL of fresh or frozen whole blood using standard methods. RESULTS: The DNA analysis showed that 10.6% of the participants were Asp-homozygotes (Asp/Asp), 40% heterozygotes (Asp/Glu) and 49.4% Glu-homozygotes (Glu/Glu). Compared to Asp/Glu and Glu/Glu, Asp/Asp had higher levels of fibrinogen (332 +/- 46 or 329 +/- 33 vs 319 +/- 29 mg/dL, P =.029), white blood cells (6.9 +/- 0.6 or 6.5 +/- 0.3 vs 6.1 +/- 0.9 x 10(3) counts, P =.044), and oxidized low-density lipoprotein cholesterol (68 +/- 21 or 61 +/- 22 vs 59 +/- 20 mg/dL, P =.039), after controlling for several potential confounders. An insignificant association was found between homocysteine (P =.08), C-reactive protein (P =.096), and the distribution of G894T polymorphism (P <.1). No association between the distribution of the polymorphism and hypertension status of the participants was observed. CONCLUSIONS: Our results imply that G894T polymorphism of the endothelial nitric oxide synthase gene is associated with elevated levels of inflammatory and oxidative stress markers, which may partially explain the increased prevalence of G894T polymorphism among patients with cardiovascular disease.