The development of a population balance model accounting for cell adaptation to a fluctuating environment is focussed in this article. In a bioreactor, the substrate concentration field and the bioreaction kinetics are strongly coupled. The latter are determined by the intensity and magnitude of concentration fluctuations encountered along the cell trajectory. Modeling these interactions between hydrodynamics and biology in heterogeneous bioreactors is a major challenge. This model is based on a previous work regarding the dynamic response of bioreactors. It is shown that a simplified population balance equation considering only growth and adaptation is sufficient to reproduce the population growth rate dynamics in batch and continuous cultures. Finally, a validation of the model implementation in a computational fluid dynamics software is proposed. The model developed in the homogeneous case now allows the numerical scale-up of a bioreactor, for it connects the population state to the concentration changes experienced. (C) 2012 American Institute of Chemical Engineers AIChE J, 59: 369-379, 2013