The broad goal of this research is to measure the rates at which gases, ions and un-ionized molecules involved in respiratory exchanges move between the red cell interior and environment, in man and animals, in health and in disease. A more distant goal is to determine if any particular exchange is rate limiting and if this rate can then be used to make measurements of the capillary bed in vivo. A major portion of the work will involve the application of rapid-reaction apparatus, stopped-flow and continuous flow, using PCO2, pH and PO2 electrodes as well as spectrophotometry for analysis, to study fast exchanges of red blood cells. We will measure the red cell permeability to ions, such as OH-, HCO3- and C1-, with which we will develop a mathematical description of exchanges within the blood during CO2 and O2 transport. We will measure the red cell permeability to weak acids and bases, both for the intrinsic value of the data and to provide information about the structure of the membrane. We will try to determine the effective carbonic anhydrase concentration inside the red cell (hemolysate) and investigate the reason for the slow rate of dissociation of HbO2 produced by a change in pH (Bohr Shift), carbamate or step decrease in PO2. Both by experimental observations and computer calculations we will inquire into the speed of readjustment of plasma pH during and after blood gas exchanges, and determine the magnitude of any lack of equilibrium between cells and plasma in an acute animal preparation. We will explore the importance of ion binding to hemoglobin in changing the Donnan effect during osmotic volume changes in the red cell and the possibility of measuring tissue PO2 from the capillary exchanges of 18O2.