BACKGROUND: Bipolar membrane electrodialysis (BMED) has been widely used for desalination, concentration, separation, and purification in many fields. The purpose of this study is to optimize the operation conditions using response surface methodology (RSM) for the regeneration of sulfuric acid and ammonia from ammonium sulfate solution by BMED coupled with ammonia in situ stripping. RESULTS: A three-factor central composite design of RSM was used to analyze the effect of operation conditions (current density, flow rate, initial acid concentration) on average current efficiency (ACE) and establish the optimal operation conditions. The ACE was 76.7 +/- 2.2% under optimal operation conditions (current density 23.8 mA cm(-2), flow rate 27.3 L h(-1), initial acid concentration 0.09 mol L-1). CONCLUSION: A suitable regression model for predicting ACE within the ranges of variables used was developed based on experimental results. The operation conditions were optimized by RSM and the ACE obtained under the optimal operation conditions was in good agreement with the value predicted by the regression model (78%), which proved the validity of the model. (c) 2007 Society of Chemical Industry.