Colloid osmotic pressure (COP) and pH were measured on the true plasma of human blood from five subjects tonometered with different concentrations of carbon dioxide. Measurements were also made on their separated plasma. COP (mmHg) of true plasma obtained from tonometered whole blood varied in proportion to the bicarbonate concentration (mEq/l): COP = 0.056 [HCO3-] + 23.3. In separated plasma, as CO2 concentration increased, COP decreased as pH decreased: COP = 1.99 (pH) + 11.0. When the change in COP due to the change in pH was subtracted from the observed change of COP due to CO2 exposure of whole blood, the difference was the change of COP due to the shift of fluid between plasma and red cells: COP adjusted for pH = 0.131 [HCO3-] + 21.5. The COP values of tonometered whole blood and separated plasma are taken to be equal at a pH of 7.40 (at the mixed venous point). The change in COP, adjusted for pH, for a given change in pCO2 is in keeping with the amount of fluid shift calculated from the measured changes in hematocrit and plasma protein concentration. An error in a previous paper (Kakiuchi et al., J. appl. Physiol. 44, 474-478, 1978) had led to an overestimation of the COP change from the exposure of whole blood to CO2 in vitro.