A flowsheet synthesis methodology is presented for the design of fractional crystallization processes. The methodology is based on four interconnected/nested networks. The first network is derived by identifying a set of thermodynamic states providing a basis for feasible separation alternatives. In this network, the nodes correspond to multiple saturation points, solute intermediates, and process feeds and end products. The second network type represents the variety of tasks that can be performed at each multiple saturation point. These tasks include cooling crystallization, evaporative crystallization, reactive crystallization, dissolution, and leaching. Heat integration is incorporated using the transshipment formulation to represent the heat exchanger network. The fourth network represents the filtration and cake washing alternatives. The cake wash and task networks are modeled using disjunctive programming and then converted into a mixed-integer program. The method is applied to the design of three salt separation example problems. The optimal design costs are seen to depend on design parameters such as product impurity level and liquid retention in the cake. The advantage of an integrated synthesis approach is demonstrated. (C) 2004 Elsevier Ltd. All rights reserved.