The monocarboxylate transporter (MCT), the sodium-bicarbonate cotransporter (NBC) and the enzyme carbonic anhydrase (CA) can coexist in the same cell e.g. epithelial and glial cells where they play a crucial role in acid/base transport and proton buffering. In the present study we investigated the interactions between these three proteins by expressing or injecting them in Xenopus oocytes and measuring changes in intracellular H⁺ and Na⁺ concentration, and the membrane current under voltage-clamp conditions. Coexpression of NBC together with the MCT1 leads to an increase of lactate-induced acid/base flux in the presence of CO₂/HCO₃^-. Injection of CA increased the rate of H⁺ change following addition of CO₂/HCO₃^-. In NBC-expressing oocytes, injection of CA augmented the membrane current while addition and removal of CO₂/HCO₃^-, indicating increased NBC transport activity in the presence of CA. In MCT1 expressing oocytes injection of CA increased the rate of acid/base change as induced by lactate not only in CO₂/HCO₃^--buffered saline, but also in HEPES-buffered saline in the nominal absence of CO₂/HCO₃^-. Our results suggest that CA and NBC both increase the activity of the MCT1 by two different mechanisms. The NBC by adding an additional buffer capacity to the oocytes cytosol, the CA by directly interacting with the membrane transporter. Supported by the DFG (De 231/16-4 and GRK 845/1).