Obesity is associated with increased cardiovascular morbidity and amortality. Endothelial dysfunction, involved in the pathogenesis of cardiovascular events, has been demonstrated in obese patients with invasive techniques requiring artery catheterization. The aim of our investigation was to evaluate, with a non-invasive method readily employable on clinical grounds, impaired vasodilatation and its relationship with insulin resistance in uncomplicated obesity. 15 uncomplicated obese subjects (BMI = 36.6 +/- 3.2) and 10 lean controls (BMI = 22.9 +/- 1.25) were enrolled in this study. All subjects underwent measurement of endothelium-dependent (FBFr) vasodilatation by forearm venous occlusion pletysmography after increasing times of ischemia, and measurement of insulin sensitivity by the euglycemic hyperinsulinemic clamp technique (M index), by fasting glucose and insulin (HOMA-IR) and by oral glucose tolerance test (ISI index). Endothelium-independent (N-FBFr) vasodilatation was assessed as well. The FBFr was markedly blunted in obese patients versus lean controls (30 s: 2.12 +/- 0.34 vs. 3.63 +/- 0.22, P < 0.01; 60 s: 2.34 +/- 0.42 vs. 3.82 +/- 0.53, P < 0.01; 180 s: 3.20 +/- 0.45 vs. 7.15 +/- 0.35, P < 0.01; 300 s: 4.08 +/- 0.94 vs. 14.1 +/- 0.82, P < 0.001). The N-FBFr was not different in the two groups. High correlation was found between M index and FBFr at all ischemia times. HOMA-IR and ISI were not related with FBFr. The non-invasive evaluation of endothelial dysfunction by a simple and reliable method based on venous occlusive plethysmography shows high correlation between impaired endothelium-dependent vasodilatation and insulin resistance in uncomplicated obesity. This non-invasive test of endothelial function may be routinely performed in the assessment of cardiovascular risk in uncomplicated obesity.