We have previously demonstrated, in primary cell cultures of chick proximal tubules, a parathyroid hormone and forskolin-activated short circuit current (I_SC) response. These currents were in the direction of apical to basolateral and were sensitive to Cl^- ion substitution and to Cl^- channel blockers, suggesting net chloride secretion, possibly mediated by a cystic fibrosis transmembrane regulator (CFTR) channel. However, this I_SC response was also blocked by the Na⁺ /H⁺ exchange (NHE) inhibitor, EIPA, indicating an interaction between these two transport pathways. To test the possibility that the EIPA effect was secondary to changes in intracellular pH, we performed basolateral permeabilization studies, using the cationic ionophore, amphotericin B (10 mM), thus clamping the intracellular pH to that of the external bathing solution (7.5). Monolayers were then stimulated with 1.0 mM forskolin to activate the chloride I_SC response, with or without EIPA on the apical side. Current-voltage relations (I-V curves) were generated after each addition. Addition of forskolin stimulated the I_SC by 19.4 +/­ 3.1 mA/cm² in the permeabilized monolayers, similar to the effect seen in intact monolayers. EIPA was equally effective at blocking the forskolin-activated I_SC in these permeabilized monolayers as in intact monolayers, suggesting that a change in pHi cannot account for its effect on Cl^- secretion. Although forskolin increased the I_SC, I-V curves revealed a decrease in slope (conductance) of 19 +/­ 4% from the pre-forskolin value. These findings suggest a linkage between NHE and CFTR activities in these cells, independent of changes in pHi. Supported by NSF IBN 03433478