The theory of a two-tank cascade of bioreactors developed by Mantzaris et al. (1998) was used to calculate the performance of such a cascade predicted by two chemically structured models: one for gene expression of Bentley and Kompala (1989) and Bentley et al. (1991) and the other a cybernetic model of Kompala et al. (1986) for multiple substitutable substrates. Two modeling approaches developed previously - one that accounts for biomass segregation and one that does not - were used with the model of Bentley and Kompala (1989) and Bentley et al, (1991). These modeling approaches showed that, in general, biomass segregation is an important feature of that happens in the second tank of the cascade and cannot be neglected. The same two approaches as well as a third approach based on the use of a chemically unstructured model were applied to the model of Kompala et al. (1986). It was found that biomass segregation in the second tank was important under some circumstances but not all and that the unstructured model failed to describe accurately what happens in the second tank under all circumstances.