To reveal the C02 diffusion process into and out of the red blood cell (RBC), changes in Pco2 following the HC03-shift were examined. The RBC suspension was mixed at 37°C with saline solution having different HC03-concentrations. In proportion to the intracellular HC03-change caused by the HC03-shift, the P02 change was increased. The rate of change increased as the hematocrit and the initial intracellular HC03-content decreased. For calculating the above Pco2 change, a theoretical equation was derived from the HendersonHasselbalch equation and the relation between both the changes in buffer base and intracellular pH. The calculated Pco2 change coincided well with the measured value, suggesting the validity of the theoretical equations.Key Words: HC03-shift, Pco2 change, Henderson-Hasselbalch equation, intracellular pH, buffer value.For clarifying C02 exchange rate in vivo, it is necessary to determine the diffusion rates of C02 and HC03-into and out of the red blood cell (RBC) as well as their interactions with oxygen. For estimating the above diffusion rates a simulation method using solutions of the diffusion equations for C02 and HC03-may be the most suitable at the present time. To solve the equations numerically, in turn, such parameters as the diffusion coefficients and the permeabilities of C02 and HC03-across the RBC membrane are indispensable. Recently, NIIZEKI et al. (1984) measured the rate of HC03-shift in the RBC in which carbonic anhydrase was not inhibited. They ascertained that the Pco2 in the RBC was increased due to HC03-influx, causing outward C02 diffusion, and the outflow of HC03-caused a decrease in intracellular Pco2 and subsequently the inward C02 diffusion. In general, the HC03-shift occurs whenever C02 molecules diffuse into or out of the RBC. Therefore, the phenomenon that the HC03-shift causes the secondary C02 diffusion is very important in obtaining the theoretical equations for the C02 and HC03-diffusions.