HCO3- secretion is a key function of secretory epithelia and involves HCO3- entry at the basolateral membrane and exit across the luminal membrane. In most epithelia the bulk of HCO3- entry is mediated by the Na+-HCO3- co-transporter NBCe1-B and HCO3- exit is mediated by the combined and regulated action of CFTR and members of the SLC26 transporters. The function and regulation of the various SLC26 transporters expressed in epithelia is beginning to emerge. In this presentation, first, the properties of several SLC26 transporters will be reviewed and second, we will discuss regulation of slc26a6 by the IP3 Receptor-binding Protein Released with IP3 (IRBIT) in the context of synergism in epithelial fluid and HCO3- secretion.