This investigation of the separation of Troger's base by the SMB process demonstrates: (1) the major importance of a proper modeling of the separation in order to determine the optimal operating conditions; (2) the need of an accurate modeling of the adsorption isotherms of the feed components. The adsorption of Troger's base onto the stationary phase ChiralPak AD was successfully described by multilayer adsorption isotherm models. Due to the complexity of these models, the region of suitable operating parameters cannot be determined algebraically by the equilibrium theory. As an alternative, the equilibrium-dispersive model, and a reliable numerical algorithm were used to scan a wide operating region, and to define this separation area. To verify the results of these calculations, the separation area was also experimentally detected by performing measurements of product purity and production rate for selected operating points. The combination of a UV detector and a polarimeter allows the accurate monitoring of the internal concentration profiles of both enantiomers. These profiles were compared to the profiles calculated using the multilayer adsorption isotherm models. In addition, the influence of the heterogeneity of the column set on the performance of the SMB process, is studied. Even under strongly nonlinear conditions, excellent agreements between calculated and experimental profiles were obtained. (C) 2004 American Institute of Chemical Engineers.