Hyperinsulinemia and insulin resistance have been extensively reported in adult patients with essential hypertension. The aim of this study was to examine serum glucose and insulin levels both in the fasting state and after 0.25 g/kg IV glucose and to relate those findings to the status of intracellular Na+ and red blood cell Na+-Li+ countertransport in a population of 21 normolipemic normotensive offspring of hypertensive parents (N-EH) and 13 control children without a history of parental essential hypertension or diabetes mellitus matched for age, body mass index, and pubertal stage. Offspring of hypertensive parents presented significantly higher serum insulin levels both after an overnight fast (17.4±1.6 versus 11.6±1.6 fiU/mh in control [mean±SEM], P<.01) and after intravenous glucose than control subjects (insulin area under the curve, 3015±310 and 2057±234 μU/mL per hour, respectively, P<.01). No relation could be established between the high red blood cell Na+-Li+ countertransport (343±22 versus 215±15 μmol/L per hour, N-EH versus control; P<.002) or high intracellular Na+ (9.8±0.28 versus 8.7 ±0.36 mEq/L, N-EH versus control) and hyperinsulinemia found in children of hypertensive parents. We conclude that the time precedence of hyperinsulinemia (and possibly insulin resistance) over the appearance of clinical hypertension in a high-risk population further supports the contention that an abnormal insulin action may play a pathogenetic role in essential hypertension. The lack of relation between hyperinsulinemia and red blood cell Na+-Li+ countertransport or intracellular Na+ suggests that either they are not linked in the causal pathway of hypertension or they are both an untimely product of a third yet undetermined pathogenetic factor.