To develop more efficient methods for production of antihypertensive peptides from Porphyra yezoensis protein, a coupled enzymatic hydrolysis and membrane separation (CEH-MS) reactor system was studied and compared with the traditional enzymatic hydrolysis (EH) and offline membrane separation (MS) method. The CEH-MS reactor was operated in three modes: batch, continuous with water feeding, and continuous with substrate feeding. The operational factors of the CEH-MS reactor had significant effect on the protein conversion degree and their optimum values were found as enzyme concentration of 0.24 g/L, temperature of 50 degrees C, pH of 9.0, time of 60 min, pump speed of 300 rpm, and substrate concentration of 4.0 g/L. Compared to the traditional method, the protein conversion degree, yield of peptides, output of peptides per unit of enzyme, and antihypertensive activity of peptides for the batch operation of CEH-MS reactor were increased by 43.6%, 43.6%, 7.7%, and 3.9%, respectively. For the continuous operation with water feeding, these data were increased by 62.7%, 62.7%, 22.1%, and 4.4%, respectively. The output of peptides was increased by 216.9% for the continuous operation with substrate feeding. In general, the CEH-MS reactor was found to be more efficient than the traditional process in terms of high utilization rate of raw material and yield of peptides. (C) 2014 Elsevier Ltd. All rights reserved.