Obesity is associated with an increased risk of developing atherosclerosis and atherosclerotic lesions are essentially an inflammatory response. The aim of this study was to evaluate the effect of a medically supervised, multidisciplinary weight loss program on endothelial functions and circulating levels of proinflammatory cytokines in obese women. Twenty healthy pre-menopausal obese women and 20 age-matched normal weight women were studied. Endothelial functions were assessed by evaluating the response of blood pressure and platelet aggregation to an intravenous bolus of L-arginine (3 g), the natural precursor of nitric oxide. In obese women, the vascular and rheological responses to L-arginine were significantly lower (p < 0.05) at baseline, as compared with non-obese women, indicating endothelial dysfunction; on the contrary, basal concentrations of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were significantly higher (p < 0.01). After one year of a multidisciplinary program of weight reduction consisting of diet, exercise and liposuction surgery, all obese women lost at least 10% of their original weight (10.5 +/- 1.7 kg, range 7.9-13.9 kg). Compared with baseline, sustained weight loss was associated with reduction of cytokine (p < 0.01) concentrations and with improvement of vascular responses to L-arginine. In conclusion, a multidisciplinary approach aimed at inducing a sustained reduction of body weight in obese women is feasible and is associated with improvement of endothelial functions and reduction of circulating proinflammatory cytokine concentrations.