Clustering of cardiovascular risk factors is thought to occur early in life. The endothelium is an important regulator of microvascular function. We investigated the relationship between microvascular function and cardiovascular risk factors in 145 normal, healthy children aged 11-14 years. Skin microvascular responses, measured using laser Doppler imaging, to iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP), were negatively correlated with percentage body fat (r = -0.20, P < 0.05 and r = -0.18, P < 0.05, respectively). Subjects were stratified into quintiles based on 2-h, post-feeding glucose levels. Subjects in the upper glucose quintile (range 7.4-11.4 mmol 1 -1) showed significantly lower vasodilatation to both ACh (P < 0.005) and SNP (P < 0.02) than those in the lower quintile (range 3.9-4.9 mmol 1-1). Waist-to-hip ratio and the fasting insulin resistance index were significantly greater in subjects in the upper quintile than those in the lower quintile (P < 0.001 and P < 0.05, respectively): Additionally, in subjects in the upper glucose quintile, fasting triglyceride correlated with fasting insulin (r = 0.59, P < 0.001) and with the fasting insulin resistance index (r = 0.49, P < 0.009), and plasma levels of cholesterol and 2-h glucose were also correlated (r = 0.40, P < 0.05). In a cross-section of normal children, microvascular function was negatively associated with adiposity. Additionally, in a subgroup of subjects, there was a clustering of high post-feeding glucose, impaired microvascular function, increased insulin resistance and higher central fat distribution. These findings suggest that risk factors for adult cardiovascular disease begin to cluster in normal children, which might have important consequences for development of atherosclerosis later in life.