Among young normotensive men, a reciprocal balance between cardiac output and sympathetic nerve activity is important in the regulation of arterial pressure. In young women, the balance among cardiac output, peripheral resistance, and sympathetic nerve activity is unknown. Consequently, the aim of this study was to examine the relationship of cardiac output and total peripheral resistance to muscle sympathetic nerve activity in young women. Multiunit peroneal recordings of muscle sympathetic nerve activity were obtained in 17 women (mean+/-SEM: age 24+/-3 years) and 21 men (mean+/-SEM: age 25+/-5 years). Mean resting muscle sympathetic nerve activity was lower in women compared with men (19+/-3 versus 25+/-1 bursts minute(-1); P<0.05), as was mean arterial pressure (89+/-1 versus 94+/-2 mm Hg; P<0.05). Mean arterial pressure was not related to muscle sympathetic nerve activity in men (P=0.80) or women (P=0.62). There was a positive relationship between total peripheral resistance and muscle sympathetic nerve activity (r=0.62; P<0.05) and an inverse relationship between cardiac output and muscle sympathetic nerve activity (r=-0.69; P<0.05) in men. Unexpectedly, muscle sympathetic nerve activity had no relationship to either total peripheral resistance (r=-0.27; P>0.05) or cardiac output (r=0.23; P>0.05) in women. Our results demonstrate that men and women rely on different integrated physiological mechanisms to maintain a normal arterial pressure despite widely varying sympathetic nerve activity among individuals. These findings may have important implications for understanding how hypertension and other disorders of blood pressure regulation occur in men and women.