Abstract: A combined system of immobilized enzyme reactor and ion exchange column was employed for hydrolysis of Penicillin G to 6 -Aminopenicillanic acid with continuous removal of Phenylacetic acid . In the composite system, the time required for 95% Penicillin G conversion to 6 -Aminopenicillanic acid could be reduced by 10. 8% and 53% of Phenylacetic acid could be removed from the reaction mixture. Based on Phenylacetic acid and Penicillin G dynamics in ion exchange process and immobilized enzyme kinetics, the hydrolysis of Penicillin G was simulated well by computer from the mathematical model developed.