The seawater reverse osmosis (RO) desalination is an attractive and viable method for the production of fresh water in many areas. This paper addresses the optimal design of RO desalination system considering membrane cleaning and replacing during the 5-year maintenance period, and only a single stage configuration with pressure exchanger is analyzed. A mathematical model for the prediction of the performance of RO process is presented in detail. Simultaneously, this paper also addresses the new fouling model and the criterion of cleaning and replacing. Then the relevant economic models to the RO desalination process are developed, which relate the cost of investment and operation with the design variables, the structural variable, as well as the binary variable that determine the membrane regeneration. The optimum design problem can be formulated as a mixed-integer non-linear programming (MINLP) problem, which minimizes the total annualized cost. The mathematical programming problem is solved with GAMS software. As a result, the optimal operational parameters and the optimal cleaning and replacing scheduling are given. According to this model, one example is solved to illustrate the advantage and effectiveness of the suggested method. (c) 2006 Published by Elsevier B.V.