The erythrocyte Cl-/HCO3- anion exchanger (AE1, Band 3) and the enzyme carbonic anhydrase (CA) catalyze interconnected processes involved in bicarbonate metabolism. The high activity form of carbonic anhydrase, CAII binds to an acidic motif located within the carboxyl-terminal tail of anion exchangers via its basic amino-terminal region. CAII is thereby positioned at the cytosolic surface of the membrane, ideally placed to catalyze CO2 hydration and to channel bicarbonate to or from the anion exchanger. This association of a soluble enzyme and a membrane transporter may be an example of a metabolon, a weakly associated complex of sequential metabolic enzymes.