The rate at which CO displaces oxygen from combination with hemoglobin in intact red cells was measured spectrophotometrically in whole blood thin films that minimize unstirred layer extra-cellular diffusion barriers. A step-change was made in CO tension from zero to one of four values (2, 7, 21 and 70 Torr) during a constant background of one of eight O2 tensions (0, 40, 70, 100, 153, 214, 285 and 428 Torr). For PO2 greater than 100 Torr measured red cell initial CO uptake rates were compared with calculated rates at the same PCO-PO2 based on the Gibson-Roughton rate equation (Gibson and Roughton, Proc. R. Soc. B 143: 310-334, 1955) for a well mixed Hb solution. Measured CO uptake rates expressed as initial rate of saturation change (delta S/delta t) quantitatively followed the theoretical rate equation (time in seconds) [sequence: see text] These measurements provide new values for theta CO, the specific conductance of whole blood (ml.min-1.Torr-1; PCO, PO2 in Torr): [sequence: see text] These results signify that in vivo, in normoxia and hyperoxia, red cell CO uptake rate is wholly reaction rate limited and that pulmonary capillary red cell CO diffusion equilibrium is rapidly achieved. The Bohr-Krogh assumption that red cell PCO = 0 during CO uptake is untrue.