The goal of this study was to investigate the activity of the Na+/H+ exchanger in erythrocytes of patients with essential hypertension and its relation with urinary Na+ excretion. The study was performed in cells from 27 untreated hypertensive patients and 30 normotensive controls with similar age and sex distribution. All subjects were studied after 4 days on a controlled Na+ diet (145 mmol/day). The activity of the Na+/H+ exchanger was determined by acidifying cell pH and measuring the initial rate of the net Na(+)-dependent H+ efflux. The activity of the Na+/H+ exchanger was higher in hypertensive patients than in controls (301 +/- 45 v 162 +/- 23 mmol/L cells/h, mean +/- SEM; P < .01). With the upper limit of the normotensive population as a cut-off point (385 mmol/L cells/h), a subgroup of 12 hypertensive patients had an abnormally high activity of Na+/H+ exchanger. Compared with controls and with patients with normal exchanger activity, patients with increased exchanger activity were characterized by lower net (P < .01) and fractional (P < .05) Na+ excretion. The accumulative Na+ balance was higher (P < .01) in hypertensive patients with increased activity of the exchanger (39.90 +/- 3.47 mmol) than in the remaining hypertensive patients (0.59 +/- 6.96 mmol) or in the normotensive population (-5.71 +/- 6.12 mmol). After analyzing the relationship of renin activity with Na+ excretion it was observed that renin activity was inappropriately low in 9 (75%) patients with increased exchanger, in 6 (40%) patients with normal exchanger, and in 6 (20%) normotensives, these differences being significant (P<.01).