The renal collecting duct is composed of principal and intercalated cells, which serve to control the extracellular fluid volume and play an important role in acid base balance. Previous studies have shown pH sensitive Cl^– currents in a variety of mammalian epithelia, including the collecting duct (Estevez et al, 2001, Nobles et al, 2004 and Yoshikawa el at, 1999). The aim of the following study was to examine the effect of pH on a Cl^– conductance in a cultured mouse collecting duct cell line (M8). Cl^– currents were examined in whole cell patches with symmetrical CsCl solutions, with a low pipette Ca²⁺ concentration. Clamp potential was stepped from a holding value of -40mV, to between +100 and -100 mV in 20mV steps. The current sensitive to 100 μM DIDS was measured in the presence of intracellular and extracellular solutions of varying pH (pH 7.4, 6.2 or 8.2). All values are expressed as means ± SEM. Statistical significance was tested using ANOVAs and assumed at the 5% level. At pH 7.4 the outward conductance (Gout) was 305 ± 105 μS/cm² (n=18) and the inward conductance (Gin) was 54.8 ± 25.9 μS/cm² (n=18). In unpaired cells, changing extracellular pH to 6.2 increased both Gout and Gin, 903 ± 204 μS/cm² (n=16) and 189 ± 58.8 μS/cm² (n=16), respectively. Increasing bath pH to 8.2 was without effect. In a separate series of experiments increasing intracellular pH to 8.2 from 7.4 decreased Gout from 572 ± 113 μS/cm² (n=28) to 192 ± 95.6 μS/cm² (n=12) and Gin from 97.2 ± 17.1 μS/cm² (n=28) to 15.73 ± 4.66 μS/cm² (n=12), at pH 7.4 and 8.2, respectively. Decreasing intracellular pH to 6.2 was without effect. These data indicate that cultured mouse collecting duct cells contain an outwardly rectifying Cl^– conductance, which is sensitive to both extracellular and intracellular pH. Given the role of the collecting duct in acid base balance this pH sensitivity could be important in collecting duct function.