In the cultivation of genetically engineered microorganisms, cell growth decreases after induction, and it becomes eminent when a product such as beta-galactosidase is harvested, indicating that conventional repeated fed-batch operation cannot be used to increase productivity. In this study, the use of multiple fermentors to overcome such difficulties was attempted. A mathematical model was developed based on fed-batch experiments using Escherichia coli JM103 harboring the pUR2921 plasmid encoding the beta-galactosidase structural gene. Computer simulation demonstrated that improved performance can be attained by repeated fed-batch operation using multiple fermentors. Experiments were then conducted to ascertain the operating conditions.