Salt gradients can be used to improve the efficiency of ion-exchange separations in simulated moving-bed systems. The gradient, formed by the use of feed and desorbent solutions of different salt concentrations, introduces regions of increased and decreased affinity of, for example, proteins for the matrix. Several gradient shapes can be formed, depending on the flow-rate ratios and salt concentrations used. Only some of these effectively increase throughput or decrease desorbent consumption. Correct gradient positioning is essential, but not trivial, because salt is adsorbed in the resin. A procedure developed selects the flow-rate ratios that allow correct positioning of gradients based on wave theory and incorporates the nonlinear Donnan isotherm of salt on ion-exchange resins. Predictions are verified by experiments combined with a mathematical equilibrium stage (true moving-bed) model. Upward and downward gradients are compared with respect to the use of desorbent and salt.