The effect of chronic acid loading on the activity of luminal membrane Na(+)-H+ exchange and basolateral membrane Na+/HCO3- cotransport and Cl(-)-HCO3- exchange was investigated using membrane vesicles isolated from rat renal cortex. Na(+)-H exchange activity was increased approx. 50% in brush-border membranes isolated from acidemic compared to control kidneys. Na+/HCO3- cotransport and Cl(-)-HCO3- exchange activity was increased approx. 45% and 100%, respectively, in basolateral membranes isolated from acidemic kidneys. The increased Na+/HCO3- cotransport activity resulted from an increased apparent maximal rate of transport (Vmax) with no change in affinity (Km) for Na+. In contrast to acid/base transport activities chronic acid loading had no effect on the activity of basolateral membrane Na+/dicarboxylate cotransport. These results suggest proximal tubule cells coordinately increased luminal and basolateral membrane acid/base transport activities to accommodate an adaptive increase in the capacity for transcellular bicarbonate reabsorption.