BACKGROUND: Obesity and high blood pressure (BP) commonly coexist in patients, and both conditions are associated with elevated sympathetic nervous activity. We tested whether the sympathetic nervous system was differently affected in men and women by the body mass index (BMI), BP, leptin and weight loss. METHODS: We measured muscle sympathetic nerve activity (MSNA, microneurography), BP and plasma leptin concentrations in 167 age-matched normotensive and hypertensive men and women divided into three subgroups: lean, BMI < 25 kg/m; overweight, BMI ≥25 and < 30 kg/m; and obese, BMI ≥30 kg/m. These measurements were repeated in a subgroup of 19 obese subjects who underwent a 12-week diet. RESULTS: Women with hypertension had increased MSNA compared with their normotensive counterparts (37 ± 2 versus 25 ± 2 bursts/min, analysis of variance, P < 0.001) and MSNA was significantly related to BP (P < 0.05, r = 0.236) but not to BMI. MSNA in men with hypertension was no different from that in normotensive subjects (33 ± 2 versus 30 ± 2 bursts/min), but MSNA was significantly related to BMI (P < 0.05, r = 0.249). Diet resulted in the same degree of weight loss in men and women, but induced a decrease in MSNA only in men (43 ± 3 to 34 ± 3 bursts/min, P < 0.01). The plasma leptin concentration was higher in women than in men, and for both groups it was related to BMI not BP (r = 0.497, P < 0.001 in women and r = 0.483, P < 0.001 in men). CONCLUSION: These data demonstrate a gender difference in the regulation of the sympathetic nervous system, in which MSNA mainly relates to BP in women and to BMI in men.