To investigate the effects of uremia on cellular function the activity of the sodium-dependent chloride-bicarbonate exchanger (sodium-dependent Cl-/HCO3- exchanger) and the sodium-independent chloride-bicarbonate exchanger (sodium-independent Cl-/HCO3- exchanger) were examined in lymphocytes from 25 patients with mild chronic renal failure, 9 patients with end-stage chronic renal failure on regular hemodialysis, and from 25 age-matched healthy control subjects. Cytosolic pH (pHi) and the activity of the sodium-dependent Cl-/HCO3- exchanger and the sodium-independent Cl-/HCO3- exchanger were measured spectrophotometrically using the pH-sensitive fluorescent dye 2'7'-bis-carboxyethyl-5 [6]-carboxyfluorescein acetoxy-methylester (BCECF-AM). The activation of the sodium-dependent Cl-/HCO3- exchanger by removal of extracellular chloride was prevented in the presence of 500 micromol/liter 4,4' diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) or in the absence of extracellular sodium, but was not affected by the specific inhibitor of the sodium/proton exchanger, ethyl isopropyl amiloride (EIPA). The sodium-dependent Cl-/HCO3- exchangers were significantly different in lymphocytes from healthy control subjects, patients with mild chronic renal failure, and patients with end-stage chronic renal failure (X2 = 6.43, P = 0.040 by Kruskal-Wallis-test). The sodium-dependent Cl-/HCO3- exchanger was significantly lower in patients with end-stage chronic renal failure compared to patients with mild chronic renal failure or compared to healthy control subjects (each P < 0.05). In patients with chronic renal failure a significantly negative correlation between sodium-dependent Cl-/HCO3- exchanger and the serum creatinine concentration (r = -0.507; P = 0.0022) could be observed. On the other hand, resting pHi in lymphocytes and sodium-independent Cl-/HCO3- exchanger were not significantly different in lymphocytes from healthy control subjects, patients with mild chronic renal failure or patients with end-stage chronic renal failure. The present study suggests that the activity of the sodium-dependent Cl-/HCO3- exchanger is progressively impaired in chronic renal failure.