Coupled entry of Na+ and Cl- into the cell may mediate salt and water absorption by the renal proximal tubule. Other leaky epithelia have been shown to have parallel luminal Na+-H+ and Cl- -OH- exchangers that can serve in concert as a major pathway for NaCl absorption. Experiments were designed to test whether Cl- -OH- or Cl- -HCO3- exchange occurs in the isolated perfused rabbit proximal convoluted tubule and thereby whether neutral transcellular NaCl absorption could be a possible mode of active transport in this segment. The studies described here make use of a lumen-to-cell gradient for Cl- to drive OH- from cell to lumen, causing an increase in the rate of H+ disappearance from the luminal fluid. Superficial proximal convoluted tubules were perfused in vitro with acidic solutions (pH 6) that were generally free of organic solutes. The bathing solution contained organics, colloid, and less than 10% of perfusate H+ concentration. H+ disappearance was calculated from the difference in pH between perfused and collected fluid, flow rate, and buffer capacity of the perfusate. The removal of Na+ from perfusate and bath reduced H+ efflux to 68% of control, a smaller effect than that noted previously in the presence of organic solutes. When Na+-containing solutions were used, bilateral replacement of Cl- by NO3-, isethionate, or SO2-(4) failed to reduce H+ efflux, but rather resulted in a 11% increase in H+ flux.(ABSTRACT TRUNCATED AT 250 WORDS)