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Na+-stimulated H+ movement and H+-stimulated Na+ uptake were studied in basolateral (blLPM) and canalicular (cLPM) rat liver membrane vesicles. H+ movement was monitored with the fluorescent amine acridine orange; 22Na uptake was assayed by a rapid Millipore filtration technique. In blLPM, inwardly directed Na+ gradients stimulated H+ efflux and outwardly directed Na+ gradients stimulated proton influx. Outwardly directed proton gradients (pH in 5.9/pH out 7.9) stimulated initial 22Na uptake rates 5- to 10-fold over pH-equilibrated conditions (pH in 7.9/pH out 7.9). Conversely, inwardly directed proton gradients (pH in 7.9/pH out 5.9) inhibited 22Na uptake. pH-dependent 22Na uptake was inhibited by amiloride and harmaline but not by other transport inhibitors, bumetanide, furosemide, 4,4'-diisothiocyano-2,2'-disulfonic acid stilbene, 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid, and …