In solute fractionation by ultrafiltration, concentration polarization increases the transmission of the components and, consequently, decreases the separation selectivity. Several techniques have been explored to increase the selectivity. Hybrid membrane cell is a concept that has been developed having in mind this purpose. Membrane-solute electric interactions determine, in a great part, the fractionation selectivity, when macromolecules to be separated have similar molecular weight, generally macromolecules difficult to separate by ultrafiltration. The purpose of the present work is to explore, by numerical simulation, the potential of a hybrid membrane cell composed by: 1-membranes electrically charged and impermeable to the solutes; and 2-membranes electrically charged and selective, alternating along the cell, to fractionate two macromolecules with similar molecular weight (e.g., Iysozyme/Dextran-T10). The apparent selectivity of the fractionation using a hybrid cell with electrically charged membranes is significantly higher (2.4), relatively to using a conventional cell (1.1). While lysozyme is repelled by electric interactions, Dextran-T10 accumulates along the impermeable membranes surface and is removed through the selective membranes located downstream. In conclusion, the hybrid cell with electrically charged and selective membranes is an advantageous method to separate two macromolecules with similar MW, provided they have opposite electric charges. (C) 2013 Elsevier B.V. All rights reserved.