The increased red blood cell Li+/Na+ exchange found in a subgroup of patients with essential hypertension (EH) may reflect an increased activity of the Na+/H+ exchange. The maximal velocity of the red cells' Na+/H+ (Na+ influx promoted by an outward H+ gradient) and Li+/Na+ (Li+ efflux promoted by external Na+) exchange were therefore measured in 41 EH and in 21 normotensive controls (NT). Both transporters were significantly higher in EH than in NT (74 +/- 39 mmol/L cell x h v 43 +/- 27 for the former, P less than .03, and 0.35 +/- 0.16 v 0.26 +/- 0.10 for the latter, P less than .05). Even though more than 100 times faster, Na+/H+ exchange was weakly but significantly correlated to Li+/Na+ exchange (r = 0.29, P less than .05). Proximal tubule Na+ reabsorption (fractional renal Li+ reabsorption) was significantly greater in EH than in NT (0.78 +/- 0.07, n = 32, v 0.73 +/- 0.06, n = 10, P less than .05) but it was not correlated to either the red cells' Na+/H+ or Li+/Na+ exchanges. Therefore, hyperactivity of Na+/H+ exchange in EH may play a role in blood pressure elevation through mechanisms other than stimulation of renal Na+ reabsorption.