BACKGROUND Sympathetic activation promotes insulin resistance and arterial hypertension with increasing adiposity. A difference in the relationship between adiposity and sympathetic activity between women and men could contribute to the known gender difference in cardiovascular disease risk. OBJECTIVE We tested whether muscle sympathetic nerve activity (MSNA) is correlated differently with waist circumference, waist to hip ratio (WHR), and body mass index (BMI) in women and men. METHODS We pooled data from two microneurography centers (Berlin, Germany; Gdansk, Poland) for a cross-sectional study. METHODS We studied 111 normotensive, healthy Caucasian subjects (70 males and 41 females). Age ranged between 19 and 62 yr and BMI ranged between 18 and 40 kg/m(2). METHODS No intervention was applied during the study. METHODS Supine heart rate, blood pressure, and MSNA were recorded after at least 30 min rest. RESULTS MSNA in bursts per minute was age dependent in both sexes [r (male) = 0.56, r (female) = 0.34, P < 0.01]. Controlling for waist and hip circumferences, age dependence remained highly significant in men (r = 0.43) and women (r = 0.43). Adjusting for age, in men, waist circumference (r = 0.29), WHR (r = 0.39), and BMI (r = 0.31) were predictive for MSNA and directly correlated (P < 0.01) but not in women. Adjusting for BMI, in men, only WHR (r = 0.40) remained predictive for MSNA. CONCLUSIONS These data support the hypothesis of a gender difference in the regulation of the sympathetic nervous system, in which MSNA mainly relates to WHR in men but not women. The phenomenon may contribute to the sexual dimorphism in cardiovascular disease risk.