The effects of oral glucose challenge on plasma glucose concentration, plasma insulin concentration, arterial blood pressure, cytosolic pH (pHi), cytosolic free Na+ concentration ([Na+]i), and cellular Na(+)-H+ exchange activity were investigated in 16 healthy subjects. The pHi, [Na+]i, and Na(+)-H+ exchange activity were measured in intact lymphocytes by using the fluorescent dye technique. The oral glucose challenge significantly increased plasma glucose, plasma insulin, and the lymphocytic Na(+)-H+ exchange activity, measured as change of pHi per second (control [0 hours], 5.20 +/- 0.53 x 10(-3) dpHi/s; 1 hour after glucose administration, 8.28 +/- 1.07 x 10(-3) dpHi/s; 2 hours after glucose administration, 8.15 +/- 1.18 x 10(-3) dpHi/s; P = .002). The lymphocytic Na(+)-H+ exchange was significantly correlated with plasma glucose concentration (r = .357, P = .041). During steady state euglycemic hyperinsulinemic clamp, the Na(+)-H+ exchange activity was not significantly changed compared with baseline values. The study shows that changes of blood glucose levels can induce an acute increase in Na(+)-H+ exchange activity. Systolic blood pressure and Na(+)-H+ exchange activity were significantly (P < .001) but weakly correlated during an oral glucose challenge.