The SLC4 family consists of ten genes. All appear to encode integral membrane proteins with very similar hydropathy plots-consistent with the presence of 10-14 transmembrane segments. At least eight SLC4 members encode proteins that transport HCO(3)(-) (or a related species, such as CO(3)(2-)) across the plasma membrane. Functionally, these eight proteins fall into two major groups: three Cl-HCO(3) exchangers (AE1-3) and five Na(+)-coupled HCO(3)(-) transporters (NBCe1, NBCe2, NBCn1, NDCBE, NCBE). Two of the Na(+)-coupled HCO(3)(- )transporters (NBCe1, NBCe2) are electrogenic; the other three Na(+)-coupled HCO(3)(-) transporters and all three AEs are electroneutral. At least NDCBE transports Cl(-) in addition to Na(+) and HCO(3)(-). Whether NCBE transports Cl(-)-in addition to Na(+) and HCO(3)(-)-is unsettled. In addition, two other SLC4 members (AE4 and BTR1) do not yet have a firmly established function; on the basis of homology, they fall between the two major groups. A characteristic of many, though not all, SLC4 members is inhibition by 4,4'-diisothiocyanatostilbene-2,2'-disulfonate (DIDS). SLC4 gene products play important roles in the carriage of CO(2) by erythrocytes, the absorption or secretion of H(+) or HCO(3)(-) by several epithelia, as well as the regulation of cell volume and intracellular pH.