A critical issue in the modeling of aerobic bioreactors is the close interaction between fluid flow and the biological reactions. In particular, shear rate has a large effect on the broth viscosity which, in turn, affects the rate of mass transfer of oxygen from the gas to the liquid phase. We demonstrate how a generic hybrid multizonal/computational fluid dynamics (CFD) modeling approach can be applied to take account of these interactions. The approach to multizonal modeling presented characterizes the flow rates between adjacent zones, and also the fluid mechanical quantities, such as the shear stress, that have important effects on the process behavior within each zone, by means of steady-state CFD calculations. An unstructured model for xanthan gum production in a batch aerobic bioreactor is used for this purpose. The hybrid modeling approach is also applied to structured models involving distributions of cell mass within each zone.