In the present work, factorial design and response surface techniques were used in combination with modeling and simulation to design and optimize an industrial bioprocess. Alcoholic fermentation process with multiple stages was considered. The fermentation system is composed of four ideal continuous-stirred tank reactors (ICSTR), linked in series,with cell recycling. Operational conditions for maximal yield and productivity were determined with ten parameters under consideration: temperature (four stages), residence time for each stage, cell recycling concentration, and the fraction of fresh medium fed into the second fermentation stage. Initially, screening design methodology was used to evaluate the process variables which were relevant in relation to yield and productivity. Five statistically significant parameters for each response were selected and utilized in factorial design in order to optimize the process. With the models obtained from the factorial design, response surfaces were generated, and the productivity improved to 12 g/l.h (an increase of 52% in relation to the control version of the bioprocess), while maintaining the high yield of 86.28% (99.1% conversion). (C) 2000 Elsevier Science Ltd. All rights reserved.