Uremic acidosis accompanies chronic renal failure in hemodialysis patients because of a retention of nonvolatile acids. Standard bicarbonate (39 mEq/L) and acetate (38 mEq/L) dialysates do not completely correct the acidosis. The acid-base and biochemical effect of a high-bicarbonate (42 mEq/L) dialysate was evaluated in 38 patients during high-efficiency and high-flux dialysis over 12 wk. All patients were dialyzed on standard bicarbonate dialysate before the study and for 8 wk after the study. In order to monitor potential excessive alkalosis, predialysis and postdialysis arterial blood gases were measured in seven patients who initially had a normal predialysis pH. Serum chemistries revealed no significant changes in predialysis BUN, calcium, ionized calcium, or phosphorus during the 12-wk study. There was no change in postdialysis ionized calcium or phosphorus. Predialysis and postdialysis serum total CO2 (STCO2) increased over the 12-wk study (P < 0.0001). By week 12, 75% of the hemodialysis patients had an STCO2 > 23 mEq/L and no patient had an STCO2 > 30 mEq/L predialysis. After the 8-wk washout, all chemistries were no different from prestudy concentrations. Predialysis blood gases in seven patients with normal predialysis HCO3 revealed a significant increase (P < 0.009) in PCO2 and HCO3 over the 12-wk study; predialysis pH and PO2 did not change. There was no significant change in postdialysis blood gases. It was concluded that: (1) a high-bicarbonate dialysate corrects predialysis acidosis in 75% of hemodialysis patients without causing progressive alkalemia, hypoxia, or hypercarbia; and (2) predialysis BUN, calcium, ionized calcium, and phosphorus are unaffected by high-bicarbonate dialysate.