The present study was designed to examine the activity of the sodium-independent chloride-bicarbonate anion exchanger and the sodium-proton exchanger in erythrocytes of 30 normotensive and 35 hypertensive subjects and its relation to the previously reported decrease in erythrocyte pH. Erythrocyte cytosolic pH was measured by the pH-sensitive fluorescent probe 2'-7'-bis(2-carboxyethyl)- 5(6)-carboxyfluorescein. The activity of the anion exchanger was determined by acidifying cell pH and measuring the initial rate of the net sodium-independent, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid-sensitive, bicarbonate influx driven by an outward proton gradient. The activity of the sodium-proton exchanger was determined by acidifying cell pH and measuring the initial rate of the net sodium-dependent proton efflux driven by an outward proton gradient. The activity of the anion exchanger was higher in hypertensive than control individuals (18,863 +/- 1081 vs 15,629 +/- 897 mmol/L cells per hour, P < .05). The activity of the sodium-proton exchanger was higher in hypertensive than control individuals (301 +/- 45 vs 162 +/- 23 mmol/L cells per hour, P < .005). Basal erythrocyte pH was lower in hypertensive than control individuals (7.27 +/- 0.02 vs 7.33 +/- 0.01, mean +/- SEM, P < .05). With the 100% confidence (lower) limit of the normotensive population as a cutoff point, a subgroup of 11 hypertensive patients had an abnormally low erythrocyte pH (< 7.19).(ABSTRACT TRUNCATED AT 250 WORDS)