Oxygen supply and dissolved carbon dioxide (dCO(2)) stripping are two of the most important control parameters in cell culture. In this study, we investigated the effect of scale-up on the volumetric gas transfer coefficient with bioreactors of different sizes (working volume: 80 1, 500 1, 2000 L, and 10,000 L; aspect ratio: 1.0-1.6). Sparging air into water increased the volumetric oxygen transfer coefficient (k(L)alpha), an index of oxygen supply efficiency, by scale-up roughly in proportion to the depth of the water. A corresponding increase in k(L)alpha was found in a real cell culture of Chinese hamster ovary cells. dCO2 stripping efficiency was evaluated in water tests using changes in k(L)alpha(CO2), an index defined in relation to k(L)alpha.k(L)alpha-2 increased following surface aeration, but the rate of increase was reduced by scale-up, which was attributed to a decrease in the liquid surface-to-volume ratio. A similar decrease in efficiency was observed in a 2000 L bioreactor by increasing the liquid volume at constant liquid surface area. The observed scale-up effects are discussed based on a simple theoretical consideration. (c) 2009, The Society for Biotechnology, Japan. All rights reserved.