BACKGROUND Low birth weight is related to increased risk of coronary heart disease in adults and recently has been associated with vascular endothelial dysfunction in children. We investigated whether the relation between birth weight and endothelial function was still present in early adult life and whether there was an interaction with emerging risk factors. RESULTS In 315 adults (165 women, 150 men, aged 20 to 28 years), high-resolution ultrasound was used to determine endothelium-dependent and -independent vascular responses of the brachial artery. Vascular measures were related to classic risk factors (smoking history, lipid profile, blood pressure, fasting insulin, exercise capacity, body mass index, and combined risk score) and birth weight. Low birth weight was associated with reduced flow-mediated dilation (coefficient=0.18 kg(-1), 95% CI 0.004 to 0.35, P:=0.04) but not with endothelium-independent dilation. The difference in flow-mediated dilation between the top and bottom fifths of birth weight was the same as between smokers and nonsmokers. Increasing levels of acquired risk factors overwhelmed the association, and there was a significant interaction of risk score with the birth weight-endothelial function relation (coefficient of interaction term [birth weightxrisk score] = -0.12, 95% CI -0.22 to -0.03, P:=0.01). CONCLUSIONS Low birth weight is associated with endothelial dysfunction in young adults. This is most marked in individuals with lower risk factor profiles and may be relevant to the pathogenesis of atherosclerosis in later life.