In the present study, we have investigated the effects of dietary potassium depletion on the activity and distribution of the H+-ATPase in the distal nephron of the Sprague-Dawley rat. H+-ATPase activity was assessed from the change in transepithelial potential difference (Vte) in response to bafilomycin A1 during perfusion of the late distal tubule in vivo, with solutions containing inhibitors of known ion channels. Bafilomycin A1 caused a negative deflection in Vte in control animals, an effect that was significantly enhanced during potassium depletion (P < 0.01). The distribution of H+-ATPase within the population of intercalated cells was assessed using a specific monoclonal antibody (E11). Hypokalemia was associated with a highly significant redistribution of the staining pattern (P < 0. 001), with an increase in the percentage of cells displaying immunoreactivity in the apical membrane. These results indicate that dietary potassium depletion increases electrogenic H+-ATPase activity in the rat distal tubule; this may be associated with increased insertion of pumps into the apical membrane.