The self-generated oscillatory operation is employed to enhance the performance bf continuous stirred-tank bioreactors (CSTBRs). The natural oscillation is achieved by splitting a single CSTBR into two smaller ones connected in series while keeping the same total residence time. A nonlinear programming technique is used to determine the optimal residence time ratio of the cascaded CSTBRs. It is shown that the optimal steady-state performance of biological systems with Monod, Tassier, or Moser growth kinetics cannot be improved by this kind of unsteady operation. However, the operation mode of self-generated oscillation can indeed be adapted to improve the performance of biological processes that have self-inhibited substrates.