We investigated the determinants of endothelial function in 100 asymptomatic, non-diabetic, non-smokers with and without the metabolic syndrome ((MS)--defined by ATP-III criteria). Subjects with MS (n=24) had greater endothelial dysfunction (ED, P<0.001) than subjects without MS. One-way analysis of variance demonstrated a significant negative linear trend between level of ED (F=21.89; P<0.001) and number of ATP-III metabolic diagnostic criteria present in each subject. In a stepwise multivariate logistic regression model presence/absence of MS was the only independent determinant of ED (P=0.01). Age, gender, LDL cholesterol, C-reactive protein, interleukin-6 and tumour necrosis factor-alpha receptor 2 had no independent influence on endothelial function. In the absence of MS as variable there was no independent association between the remaining variables and endothelial function. Receiver operating characteristic (ROC) curves demonstrated that a combination of age, LDL cholesterol and CRP levels and presence/absence of MS can be used to predict ED (area under curve 0.81+/-0.06) and thus potentially may be used as a simple screening test to identify subjects with the greatest level of ED (sensitivity=0.82, specificity=0.72). Our study demonstrated that subjects with MS had greater ED. The extent of ED increased with presence of each additional ATP-III diagnostic criteria. Presence/absence of MS was the only independent predictor of ED and in conjunction with age, LDL cholesterol and CRP levels could be used as a potential simple clinical screening test for ED.