Increased activity of sodium/hydrogen exchange provides a potentially important mechanism for the development of hypertension. The aims of this study were to compare platelet sodium/hydrogen exchanger activity and renal acid-base excretion in normotensives and hypertensives of Caucasian origin. Platelet intracellular pH (pH i ) was measured using the fluorescent dye BCECF to monitor intracellular pH. Sodium/hydrogen exchanger activity was estimated from the recovery of pH i clamped to 6.25 with nigericin. Normotensives had supine blood pressures of <140 and <90 mmHg; those with essential hypertension had blood pressures >150/95 mmHg with no known secondary cause. Measurements of platelet pH i and sodium/hydrogen exchanger activity were made on 26 normotensives (ten female, sixteen male) and 25 hypertensives (five female, twenty male). All subjects were on their usual dietary sodium intake. Statistical analysis was by two-way analysis of variance for gender and blood pressure status. Group values are expressed as means+/-SD and a P value of <0.05 was taken as being statistically significant. There were no significant differences in platelet pH i between the normotensive (n=26) and the hypertensive (n=25) group: pH i 7.21+/-0.14 and 7.18+/-0.16, respectively. The pH i recovery after acidification was sodium-dependent and inhibited by N-hexamethylene amiloride. Comparison of kinetic constants showed no significant differences between the normotensive and the hypertensive groups: values for rate constants and initial velocities were 0.24+/-0.04 s - 1 , 0.16+/-0.03 dpH i /s for the normotensives and 0.25+/-0.05 s - 1 , 0.16+/-0.03 dpH i /s for the hypertensives, respectively; there were also no significant differences in proton fluxes. The inability to find raised platelet sodium/hydrogen exchanger in the hypertensives contrasts with previous observations using other methods for the measurement of this exchanger in platelets and this raises important methodological issues in the assessment of platelet sodium/hydrogen exchanger activity.