Insulin resistance and elevated sympathetic nerve activity (SNA) are observed in young borderline hypertensive humans. A positive family history of hypertension (FH) is a strong risk factor for developing hypertension. To assess whether insulin resistance and increased sympathetic tone precede the onset of hypertension, we studied 17 young adults with and 17 without a documented family history of hypertension. Subjects were matched for age (33+/-0.4 years in FH positive and 32+/-0.5 years in FH negative; mean+/-SE) and body mass index (BMI, 25+/-1 kg/m2 in both FH positive and FH negative subjects). We measured blood pressure (BP), heart rate (HR), muscle sympathetic nerve activity (MSNA, microneurography), forearm blood flow, and insulin sensitivity (total glucose uptake determined by an euglycemic/hyperinsulinemic clamp using stable isotope tracer infusion), and calculated forearm vascular resistance (FVR). Mean BP and HR were similar in both groups (86+/-3 mm Hg and 61+/-2 beats/min, and 85+/-2 mm Hg and 62 +/-2 beats/min, respectively, in FH positive and negative respectively, P = ns). Baseline MSNA (24 +/-3 bursts/min in FH positive v 20+/-3 bursts/min in FH negative, P = ns) and total glucose uptake [0.104+/-0.014 mg/(kg x min x microU insulin/mL) in FH positive v 0.095+/-0.014 mg/(kg xmin x microU insulin/mL) in FH negative, P = ns] did not differ between the groups. Sympathetic and vascular responses to insulin were also similar in both groups. The increase in MSNA was 10+/-2 bursts/ min in FH positive and 10+/-1 bursts/min in FH negative, P = ns. Thus, age- and weight-matched offspring with and without a FH of hypertension did not vary in MSNA or insulin sensitivity. These findings suggest that in the absence of obesity and high arterial pressure, a FH of hypertension may not be accompanied by decreased insulin sensitivity or increased MSNA.