Hepatocytes possess several mechanisms for membrane acid-base transport, which work in concert to maintain intracellular pH (pHi) in a narrow physiological range, despite metabolic processes that produce and consume substantial quantities of H+ and HCO3-.Na(+)-H+ and Cl(-)-HCO3- exchangers contribute to recovery from intracellular acidosis and alkalosis, respectively, but are largely inoperative at physiological values of pHi. Recent studies indicate that hepatocytes also possess a mechanism for coupled transport of Na+ and HCO3- across the basolateral membrane. This appears to be the dominant pathway for membrane acid-base transport operative under basal conditions, mediates influx of Na+ and HCO3-, and is an important contributor to recovery from intracellular acidosis. In this review, the properties of hepatic Na(+)-HCO3- cotransport are described with emphasis on its effects on pHi and Na+ homeostasis and on the possible role of membrane potential difference as a signal modulating the rate of HCO3- influx and pHi of hepatocytes through effects on this transporter.