Free intracellular calcium [Ca2+]i, sodium [Na+]i and potassium [K+]i were assessed in freeze-thawed human red blood cells (RBC) by ion-selective electrodes. After metabolic depletion by 30 mM 2-desoxy-glucose, [Ca2+]i increased faster and to significantly higher values in RBC from 16 patients with mild to moderate essential hypertension (mean diastolic blood pressure 111 +/- 10 mmHg) than in the RBC of 24 normotensives. The rate of [Ca2+]i increase was 7.0 +/- 3.6 versus 3.7 +/- 4.0 mumol/h/l cells (P less than 0.01) for the first 24 h and 8.1 +/- 4.8 versus 6.4 +/- 3.5 mumol/h/l cells for the following 24 h. [Na+]i before and after 24 h incubation was significantly higher in hypertensives, whereas basal [Ca2+]i and [K+]i before and after incubation were the same in both groups. After Ca loading by ionophore A 23187, the maximum rate of [Ca2+]i extrusion was not significantly lower in intact RBC from hypertensives than in those from normotensives (59.5 +/- 7.8 versus 87.9 +/- 18.1 mumol/min/l cells). These results indicate disturbances in RBC Ca metabolism similar to those observed earlier for Na and K. If generalized, the defect could lead to raised [Ca2+]i in smooth muscle and sympathetic nerve tissue, thus causing increased vascular tone and probably catecholamine release with subsequent arterial hypertension.