Components of polymer mixtures with different chemical composition can be separated by liquid chromatography by applying appropriate conditions (column packing, eluent, temperature, and pressure) in which just one type of macromolecule is eluted in the size exclusion mode while the other component is fully retained within on column packing. The feasibility of this idea has been demonstrated using the mixtures of polystyrene (PS) plus polymethylmethacrylate (PMMA) with silica gel as the column packing and toluene as an eluent. The PMMA was retained by the silica gel at ambient temperature and moderate pressures of several MPa while the PS was eluted by a typical SEC mechanism. Furthermore, the molar mass distribution of the PS could be determined in one step with the same precision as if injected alone. Surprisingly large amounts of PMMA were trapped within the column prior to its SEC characteristics being influenced. After a series of analyses the column has to be regenerated with a brief flushing with a desorbing liquid, tetrahydrofuran in the system studied. The re-equilibrization of the column with the initial eluent, toluene, was fast and a new series of analyses could be started soon after the characterization step had seen finished.