The anion exchange system of the red cell membrane resides in an integral membrane protein with a molecular mass of approximately 10(5) daltons. We report on the identification of the transport system by means of covalently binding stilbene-disulfonates. We further describe the gross molecular arrangement of the polypeptide in the membrane, as well as recent attempts to identify functionally essential amino acid side chains in the transport system. The presence of a large number of charged amino acid residues in the intramembrane segments of the protein forms the basis of a zipper model of anion exchange. The zipper is closed by salt bridges between oppositely charged residues, which mediate the anion exchange diffusion through minor conformational changes. Salt bridge gates, which are arranged in series through the permeation pathway, function in the exchange mode, because a permeating anion switches the orientation of the charges of the salt bridge between alternative positions. The energy barriers to permeation are thus altered by the passage of a mobile anion. The shift in the relative positions of the charges in the salt bridges implies that anions are admitted alternatingly from the two ends of the salt bridge array.