In erythrocytes, the extrusion of a cell sodium load is accomplished by the ouabain-sensitive sodium-potassium pump and by the furosemide-sensitive sodium-potassium cotransport, which operate against the passive sodium permeability. The precise characterization of these transport pathways requires the determination of the turnover rates of cation translocation and the affinities for substrates and effectors. The preliminary results of such kinetic study in essential hypertension is reported here. An abnormally low rate of net sodium extrusion by the sodium-potassium co-transport system was observed in essential hypertensive patients and in a high proportion of their young normotensive offspring. A normal cotransport system found in secondary hypertensive subjects devoid of familial history of hypertension confirmed that the abnormal cotransport system is not the consequence of high blood pressure per se. At the molecular level, the cotransport abnormality seems to be consecutive to a diminished apparent affinity for intracellular Na+. A 20-40% increase in the rate of net sodium extrusion by the sodium-potassium pump seems to compensate for the abnormal cotransport in erythrocytes from some young normotensive subjects born of essential hypertensive parents and from some benign essential hypertensive subjects. No difference could be detected between the passive sodium permeability of erythrocytes from hypertensive subjects and normotensive controls. In conclusion, essential hypertension seems to be associate with an inherited defect in the apparent affinity for intracellular Na+ of the sodium-potassium cotransport system. We propose therefore the laboratory study of this system for (i) the distinction between essential and secondary hypertension and (ii) the preventive investigation of young normotensive subjects in hypertensive families.