The membrane potential response of proximal tubular cells to changing HCO3- concentrations was measured in micro-puncture experiments on rat kidney in vivo. No significant effect was noticed when luminal bicarbonate concentration was changed. Changing peritubular HCO3- by substitution with Cl- resulted in conspicuous membrane potential transients, which reached peak values after 100-200 ms and decayed towards near control with time constants of approximately 2 s. The polarity of the potential changes and the dependence of the initial potential deflections on the logarithm of HCO3- concentration suggest a high conductance of the peritubular cell membrane for HCO3- buffer, but not for Cl-, SO4(2-) or isethionate. At constant pH, tHCO3- was estimated to amount to approximately 0.68. At constant pCO2, tHCO3- was even greater because of an additional effect of OH- or respectively H+ gradients across the cell membrane. The secondary repolarization may be explained by passive net movements of K+ and HCO3- across the peritubular cell membrane, which result in a readjustment of intracellular HCO3- to the altered peritubular HCO3- concentration. Application of carbonic anhydrase inhibitors in the tubular lumen reduced the initial potential response by one half and doubled the repolarization time constant. The same effect occurred instantaneously when the inhibitor was applied - together with the HCO3- concentration step - in the peritubular perfusate. This observation demonstrates that membrane bound carbonic anhydrase is somehow involved in passive rheogenic bicarbonate transfer across the peritubular cell membrane, and suggests that HCO3- permeation might occur in form of CO2 and OH- (or H+ in opposite direction).