The role of Slc26a6 (PAT1) on apical Cl^-/HCO₃^- exchange and bicarbonate secretion in pancreatic duct cells was investigated using Slc26a6 null and wild-type (wt) mice. Apical Cl^-/HCO₃^- exchange activity was measured with the pH-sensitive dye BCECF in microperfused interlobular ducts. The HCO₃^--influx mode of apical [Cl^-]_i/[HCO₃^-]_o exchange was dramatically upregulated in Slc26a6 null mice (p<0.01 vs. wt), whereas the HCO₃^--efflux mode of apical [Cl^-]_o/[HCO₃^-]_i exchange was decreased in Slc26a6 null mice (p<0.05 vs wt), suggesting the uni directionality of the Slc26a6-mediated HCO₃^- transport. Fluid secretory rate in interlobular ducts were comparable in wt and Slc26a6 null mice (p>0.05). In addition, when pancreatic juice was collected from whole animals in basal and secretin-stimulated conditions, neither juice volume nor its pH showed differences between WT and Slc26a6 null mice. Semi quantitative RT-PCR demonstrated more than 5-fold upregulation in Slc26a3 (DRA) expression in Slc26a6 ko pancreas. In conclusion, these results point to the role of Slc26a6 in HCO₃^- efflux at the apical membrane and also suggest the presence of a robust Slc26a3 compensatory upregulation, which can replace the function of Slc26a6 in pancreatic ducts.