Adjustment of bath [HCO(3)(-)] to "normalize" predialysis serum [HCO(3)(-)] in patients receiving intermittent hemodialysis has been advocated to prevent the adverse effects of metabolic acidosis. However, when mortality risk has been evaluated in hemodialysis patients in relation to their nadir serum [HCO(3)(-)], an increase in risk is noted both with very low values (<18 mmol/l) and very high values (>27 mmol/l). If mortality risk is adjusted for comorbidity, age and effectiveness of dialysis, as well as for nutritional and inflammatory factors, very low predialysis values remain an independent risk factor, but the risk for high values virtually disappears. Patients with mild predialysis metabolic acidosis (serum [HCO(3)(-)] 18-23 mmol/l) have the lowest mortality risk. Metabolic acidosis has adverse effects on bone and muscle metabolism in patients receiving hemodialysis but, unless the acidosis is severe, these effects appear to be overshadowed by nutritional and inflammatory influences. This commentary reviews the principles of acid-base homeostasis in patients receiving intermittent hemodialysis and the studies that have addressed the adverse effects of metabolic acidosis in this patient population. It concludes that high predialysis serum [HCO(3)(-)] values are likely a marker for malnutrition and comorbidity, whereas very low values may be an indication for direct treatment. The latter should be addressed using strategies to increase predialysis values, whereas the former need attention directed to nutritional factors and comorbidity.