The changes in electrical membrane parameters and intracellular sodium activity associated with the absorption of D-glucose were studied in the isolated perfused proximal tubule of the Ambystoma tigrinum kidney. The addition of 10 mM D-glucose to a substrate-free luminal perfusate depolarized the basolateral and luminal membrane potentials by -16.2 +/- 0.9 mV and +20.4 +/- 0.9 mV, respectively (P less than 0.01), increased intracellular sodium activity (acellNa) by 5.1 +/- 0.8 mM (P less than 0.01) and significantly (P less than 0.01) decreased luminal membrane resistance from 2,859 +/- 454 to 1,483 +/- 120 omega X cm2. Both the electrogenic response and the change in acellNa induced by luminal glucose were a saturating function of luminal glucose and sodium concentrations. The electrogenic response to luminal glucose was sensitive to intracellular glucose concentration and the change in acellNa induced by luminal glucose was sensitive to intracellular sodium concentrations. Within the physiological range of membrane potentials and studied, the sodium-glucose cotransporter is more sensitive to a decrease in a favorable electrical gradient than to an increase in a favourable chemical gradient for sodium across the luminal membrane.