The gene family of anion exchangers consists of at least four or five members, of which three have been characterized at the cDNA level. AE1-3 encode polypeptides that share significant homology with the erythrocyte anion exchanger, band 3 (AE1). Expression of cDNAs encoding these genes in heterologous systems confirms that this sequence similarity is reflected in the capacity to mediate reversible Cl/HCO3 exchange. While the NH2-terminal domain of band 3 is known to interact with several cytoplasmic proteins in erythrocytes, the function of the analogous domains of AE2 and AE3 remains unknown. The AE1 gene is expressed coordinately with other erythroid genes during erythropoiesis in both avian and mammalian erythroid progenitor cells. In addition, AE1 is expressed at the basolateral plasma membrane of the acid-secreting intercalated cells of the kidney. AE2 is expressed in a number of epithelial and nonepithelial cells; it may be expressed in the Golgi apparatus of some of these cells. AE3 is expressed in excitable tissues, including neurons and muscle. It is likely that these proteins play a role in regulation of intracellular pH and chloride in their respective tissue. Understanding of the physiological roles of these proteins, both for ion transport and for plasma membrane organization, remains a central issue.