Summary of work: This project focuses on the mechanism involved in regulating the binding of oxygen to hemoglobin and the transport of oxygen to the tissues. Emphasis is placed on ways in which these functions are impaired and change with age. These studies have focused on the oxidation of hemoglobin, which produces nonfunctional hemoglobin and the simultaneous release of oxyradicals. The enhancement of these oxidative processes under hypoxic conditions is being explored as a possible source of tissue and organ damage, which would be exacerbated during aging. Studies are also included which are directed at the stability of the entire erythrocyte and the erythrocyte membrane. Animal and human studies are performed to investigate possible functional impairment associated with red cell damage. The role of erythrocyte autoxidation in regulating the release of NO from nitrosothiols is being investigated.