We examined the effect of familial burden of hypertension on blood pressure (BP) levels, insulin resistance (IR), and intracellular ions in healthy offspring of Greek families with one, two, or no hypertensive parents. A total of 118 adolescents and young adults were recruited. Three groups were formed: Group A, both parents were normotensive (N-N); Group B, one parent normotensive and one hypertensive (N-H); and Group C, both parents hypertensive (H-H). BP levels, homeostasis assessment model-IR (HOMA-IR) index, and intracellular Na(+), K(+), Ca(2+), and Mg(2+) were compared in the three groups. Also, multiple regression analyses were used to create models with BP parameters and HOMA-IR as dependent variables. Offspring of H-H parents had higher body mass index (BMI) (mean difference, 4.3 +/- 0.9 kg/m(2); 95% confidence interval [CI], 2.0-6.5), higher systolic blood pressure (SBP) (mean difference, 13.2 +/- 3.1 mm Hg; 95% CI, 5.8-20.7), increased levels of intraerythrocyte Ca(2+) (mean difference, 0.02 +/- 0.01 mmol/l; 95% CI, 0.05-0.1), and fasting blood glucose (mean difference, 0.31 +/- 0.10 mmol/l; 95% CI, 0.05-0.56) when compared with those with no parental history of hypertension. In the regression model, SBP was found to be significantly affected by BMI (beta = 0.43; P < .001), iK(+) (beta = -0.224; P < .01), and gender (beta = -0.298; P < .001). The addition of the parental history showed a significant independent association of H-H parental history with SBP (beta = 0.27; P < .05). HOMA-IR was significantly determined by BMI (beta = 0.511; P < .05), iNa(+) (beta = 0.211; P < .05), and iMg(2+) (beta = -0.205; P < .05). Parental history of hypertension did not influence the HOMA-IR index. This study highlights the relative importance and contribution of environmental and genetic influences on the development of high BP. Both these influences possibly alter the intracellular ionic environment. However, nurture rather than familial hypertension burden is the key factor of IR in Greek offspring.