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^sub 3^^sup -^ (or a related species, such as CO^sub 3^^sup 2-^) across the plasma membrane. Functionally, these eight proteins fall into two major groups: three Cl-HCO^sub 3^ exchangers (AE1-3) and five Na^sup +^-coupled HCO^sub 3^^sup -^ transporters (NBCe1, NBCe2, NBCn1, NDCBE, NCBE). Two of the Na^sup +^-coupled HCO^sub 3^^sup -^transporters (NBCe1, NBCe2) are electrogenic; the other three Na^sup +^-coupled HCO^sub 3^^sup -^ transporters and all three AEs are electroneutral. At least NDCBE transports Cl^sup -^ in addition to Na^sup +^ and HCO^sub 3^^sup -^. Whether NCBE transports Cl^sup -^--in addition to Na^sup +^ and HCO^sub 3^^sup -^--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^sub 2^ by erythrocytes, the absorption or secretion of H^sup +^ or HCO^sub 3^^sup -^ by several epithelia, as well as the regulation of cell volume and intracellular pH.PUBLICATION ABSTRACT