Animal studies suggest that alkalinization and increased intake of free water both serve to decrease the rate of progression in chronic renal failure. However, clinicians have been reluctant to apply either strategy because of concerns regarding volume overload and water intoxication. We tested the effects of 2 1 daily water supplementation, with either an electrolyte-poor or a HCO3-rich (47.5 mmol/1) water in 11 patients with chronic renal failure (creatinine clearance 10 +/- 5 ml/min). The patients were brought into balance on a diet containing 80 mmol/24 h Na+, 80 mmol/24 h Cl- and 70 mmol/24 h K+. After a 3-day equilibration period, the patients were randomized to one or the other regimen for 7 days. After a 3-day washout period, the alternate regimen was given for another 7 days. Neither regimen led to weight gain or hyponatremia. The supplemental 95 mmol/24 h HCO3- lowered the serum Cl- concentration and raised the serum HCO3- concentration, as well as the pH value, to normal. Creatinine clearance and protein excretion were not affected. Serum beta 2-microglobulin concentrations decreased with the NaHCO3-containing water. Na+/H(+)-antiporter activity was not consistently influenced since an order effect of the regimens was apparent. We conclude that 2 1/24 h water and NaHCO3 supplementation is well tolerated, causes no deleterious effects, and may evoke improvement in patients with chronic renal failure.