In erythrocytes from essential hypertensive patients and some of their normotensive offspring, the Na+,K+ co-transport system is unable to transport Na+ in an uphill direction against the electrochemical Na+ gradient. Recent studies of the kinetic properties of this system have permitted us to further characterize the abnormal co-transport in hypertension. Thirty-four essential hypertensive patients were characterized by a two- to three-fold decrease in the maximal rate of the outward Na+,K+ co-transport and a partial uncoupling of this system as compared with 22 normotensive controls. On the other hand, a normal co-transport was found in five secondary hypertensives with no family history of hypertension, thus indicating that the abnormal co-transport is not the consequence of high blood pressure per se. An abnormal co-transport was also found in around 50% of 19 young normotensives born of one hypertensive parent, suggesting genetic transmission. This study allows us to propose the use of a specific Na+,K+ co-transport assay for the differential diagnosis between essential and secondary hypertension and for the detection of those normotensives born of hypertensive parents with a potential risk to develop high blood pressure.