Dissolved carbon dioxide (dCO(2)) accumulation is one of the most serious problems in the scale-up of industrial cell culture. To predict the effects of dCO(2) stripping in different culture conditions and at different scales, we examined a method of estimation of dCO(2) stripping using a model medium. The operational parameters (e.g., sparging and agitation rate) and the size of the bioreactor (working volume: 80 1, 500 1, 2000 L; aspect ratio: 1.0 similar to 1.6) were varied, and the model medium was prepared by adjusting pH, density, viscosity, surface tension, and buffer conditions. dCO(2) stripping efficiency was evaluated using the index k(L)alpha(CO2), which was defined in accordance with the volumetric oxygen transfer coefficient k(L)alpha. The model medium exhibited dCO(2) stripping behavior similar to real culture medium in all experimental conditions tested. It is expected that the use of the model medium to estimate dCO(2) stripping in real cultures will be valuable for determining the culture conditions in bioreactors in scale-up. (c) 2009, The Society for Biotechnology, Japan. All rights reserved.