A procedure for the optimal determination of process synthesis, design and operation for both batch and continuous separation is presented. The procedure allows the simultaneous determination of the optimal process from any specified available process alternatives, its configuration, its design and corresponding operation in order to perform a given separation duty. in this work, distillation, pervaporation and hybrid distillation/pervaporation processes are considered as process alternatives. The optimisation strategy takes into account an overall economic index that encompasses capital investment, operating costs and production revenues. Furthermore, rigorous mathematical models developed from first principles for distillation and pervaporation are used. Case studies are presented and it is found that hybrid distillation/pervaporation processes are the optimal synthesis solution in most cases and large costs savings can be made compared to traditional operation based on distillation alone. (c) 2007 The Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.