Residence time distribution (RTD) and internal age distribution (IAD) approaches were used to investigate complex interactions between hydrodynamics and biological activity in an innovative two-stage continuous membrane bioreactor with cell recycling. This bioprocess was designed to investigate the behaviour of yeast (Saccharomyces cerevisiae) in extreme conditions and to intensify bioproduction. Based on established RTD/IAD models, a parametric study was conducted considering biological constraints (growth rate, viability and products kinetics) under realistic working conditions (reactor volume, feed, bleed, permeate and recirculation flowrates). Competition between internal recirculation and dilution rates was observed and described by a dimensionless circulation index, K. Bioprocess performance (cell viability, substrate and ethanol concentrations) was discussed according to RTD/IAD simulations of 12 cultures. Assuming a critical residence time within the second stage enabled us to define acceptable and unacceptable working conditions to maintain biological activity. (c) 2012 Elsevier Ltd. All rights reserved.