Fed-batch fermentation for tryptophan synthetase by a recombinant Escherichia coli strain has been analyzed through a model incorporating segregational loss of the plasmid pPLc23trpA1 and imperfect macromixing of the broth. These features become significant in large fermentation vessels, where fluid circulation in the bioreactor influences the rates of cell growth and productivity. A simple model consisting of two interacting reactors describes the degree of macromixing, which is characterized by the respective (internal) dilution rates.. Controlled imperfect macromixing; is superior to other methods in arresting, and even reversing, the normal decline in the concentration of recombinant cells, thereby providing a method to exploit the non-homogeneity of the broth in large bioreactors. Some physical implications are discussed.