The main purpose of this research proposal is to elucidate the molecular mechanisms whereby an important membrane component, the anion transport system of human red blood cells, accomplishes the transfer of anions across the cell membrane. This transfer is responsible for the well known "chloride shift," which is so crucial to the CO2-carrying capacity of the blood. The relevant membrane components, i.e., 100,000 dalton polypeptides (commonly known as band 3), have been identified, isolated and functionally reconstituted by us and are presently being studied in terms of their disposition in the membrane matrix. In the present research proposal we seek to explore the molecular details of the underlying mechanism of red blood cell anion transport with the aid of fluorescent probes and of various fluorescence-spectroscopy techniques of both static and dynamic nature. The significance of the research relies on the fact that the anion transfer system provides, both conceptually and methodologically, one of the best models for studying the involvement of specific proteins in transport, particularly regarding structure-function relationships. The model could also provide useful chemical guidelines for the design of pharmacological agents whose targets are specific membrane transport systems.