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Department of Physiology and Biophysics Program, University of Virginia, Charlottesville, VA 22908, U.S.A.

1. This paper deals with the contributions of the red cell membrane and an external diffusion boundary layer (`unstirred layer') to the resistance to O₂ entry into the red cell. Bovine serum albumin (BSA) was added to the extracellular fluid to enhance the effect of the diffusion boundary layer by diminishing both the solubility and the diffusivity of O₂. The rate of O₂ uptake by human red cells at various extracellular BSA concentrations was determined with a stopped-flow rapid-reaction apparatus.

2. The initial rate of O₂ uptake by the red cells was directly proportional to the diffusion coefficient of O₂ in the extracellular fluid.

3. If the diffusion boundary layer and the plasma membrane are considered as resistors in series, we estimate that 82-100% of the total resistance to O₂ entering the cell is due to the diffusion boundary layer. Our best estimate is that 95% of the resistance resides in the diffusion boundary layer.

4. Our best estimate of the O₂ permeability of the red cell membrane is 3·15 x 10^-6 m-mole/(cm² sec mmHg). With this permeability the membrane would account for only 5% of the total resistance to O₂ entering the cell. Partly because the membrane O₂ diffusion resistance is a small fraction of the total resistance our estimate of the membrane resistance has a large standard deviation. Taking our estimate of the membrane resistance plus and minus its standard deviation we find that the membrane may account for 0-18% of the total resistance to O₂ entering the cell.

5. The effective thickness of the diffusion boundary layer immediately after mixing is about 1·93 µm according to our analysis.

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