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Lab‐scale (70 L) and industrial scale (70 m3) aerated fermenters are simulated using a commercial computational fluid dynamics code. The model combines an Euler‐Euler approach for the two‐phase flow, a population balance model for biological adaptation to concentration gradients, and a kinetic model for biological reactions. Scale‐up at constant volumetric mass transfer coefficient is performed, leading to concentration gradients at the large scale. The results show that for a given concentration field and a given circulation time tc, the population (physiological) state depends on the characteristic time of biological adaptation Ta. The population specific growth rate (Ta≫tc) is found independent of the spatial location and closely related to the volume average concentration. Oppositely, the population specific uptake rate (Ta∼tc) is spatially heterogeneous. The resulting local disequilibria between the uptake rate and the growth rate provide an explanation for the decreased performances of poorly macromixed industrial bioreactors. © 2013 American Institute of Chemical Engineers AIChE J, 60: 27–40, 2014