Background —Previous studies have shown that sympathetic cardiovascular outflow is increased in obese normotensive subjects and that this increase is associated with a baroreflex impairment. The purpose of this study was to determine whether these abnormalities are irreversible or can be favorably affected by body weight reduction. Methods and Results —In 20 obese normotensive subjects (age, 31.3±1.7 years; body mass index, 37.6±0.9 kg/m ² , mean±SEM), we measured beat-to-beat arterial blood pressure (Finapres technique), heart rate (ECG), postganglionic muscle sympathetic nerve activity (microneurography at a peroneal nerve), and venous plasma norepinephrine (high-performance liquid chromatography) at rest and during baroreceptor stimulation and deactivation induced by increases and reductions of blood pressure via stepwise intravenous infusions of phenylephrine and nitroprusside. Measurements were repeated in 10 subjects after a 16-week hypocaloric diet with normal sodium content (4600 to 5000 J and 210 mmol NaCl/d) and in the remaining 10 subjects after a 16-week observation period without any reduction in the caloric intake. The hypocaloric diet significantly reduced body mass index, slightly reduced blood pressure, and caused a significant and marked decrease in both muscle sympathetic nerve activity (from 50.0±5.1 to 32.9±4.6 bursts per 100 heart beats, P <.01) and plasma norepinephrine (from 356.2±43 to 258.4±29 pg/mL, P <.05). This was associated with a significant improvement in the sensitivity of the baroreceptor heart rate (+71.5±11%, P <.01) and muscle sympathetic nerve activity (+124.5±22%, P <.001) reflex. Total body glucose uptake also increased significantly (+60.8±12.0%, P <.05), indicating an increase in insulin sensitivity. All variables remained unchanged in subjects not undergoing caloric restriction. Conclusions —In obese normotensive subjects, a reduction in body weight induced by a hypocaloric diet with normal sodium content exerts a marked reduction in sympathetic activity owing to central sympathoinhibition. This can be due to the consequences of an increased insulin sensitivity but also to a restoration of the baroreflex control of the cardiovascular system with weight loss.