A mathematical representation of a heat-exchanger network structure that explicitly accounts for the relative location of heat-transfer units, splitters, and mixers is presented. It is the basis of a mixed-integer linear programming sequential approach to the synthesis of heat-exchanger networks that allows the designer to specify beforehand some desired topology features as further design targets. Such structural information stands for additional problem data to be considered in the problem formulation, thus enhancing the involvement of the design engineer in the synthesis task. The topology constraints are expressed in terms of (i) the equipment items (heat exchangers, splitters, and mixers) that could be incorporated into the network, (ii) the feasible neighbors for every potential unit, and (iii) the heat matches, if any, with which a heat exchanger can be accomplished in parallel over any process stream. Moreover, the number and types of splitters being arranged over either a particular stream or the whole network can also be restrained. The new approach has been successfully applied to the solution of five example problems at each of which a wide variety of structural design restrictions were specified.