In order to assess the links which are claimed to exist between peripheral insulin resistance and intracellular magnesium and calcium concentrations, we measured free intralymphocyte magnesium (Mg-i) and calcium (Ca-i) concentrations as well as the rate constant of plasma glucose disappearance (K-itt) after insulin injection (insulin tolerance test: ITT) in a group of 16 normotensive control subjects (NC) and 34 essential hypertensive subjects (EH). Mg-i and Ca-i were measured in triplicate by means of a fluorimetric technique based-on the dyes furaptra and fura-2 respectively. K-itt values proved significantly reduced in EH as compared to NC (M +/- SD, EH: 4.49 +/- 1.31 vs 5.28 +/- 1.19, P <0.05; 95% confidence limits: 0.23-1.5). Mg-i and Ca-i were not statistically different in EH as compared to NC subjects (Mg-i, NC: 266 +/- 20 mu mol/l; EH : 245 +/- 50 mu mol/l; Ca-i, NC: 47 +/- 9 nmol/l, EH: 46 +/- 13 nmol/l). We found a statistically significant inverse correlation in the whole study group between K-itt and body mass index (R= -0.363, P<0.01) and a statistically significant positive correlation between K-itt and Mg-i (R= 0.347, P=0.013) was found. In a step-up multivariate regression analysis including blood pressure, plasma lipids, BMI, plasma magnesium, fasting insulin, fasting glucose, Mg-i and Ca-i, the dependent variable K-itt is statistically significantly correlated with body mass index and Mg-i. In a first attempt to study the relationships between insulin resistance, Mg-i and Ca-i in nucleated cells, the chosen index of peripheral resistance seems to be linked to intracellular free magnesium.