A new procedure (SOS-LC) is described for the optimization of the HPLC stationary phase, using serially connected columns and the principle of the "PRISMA" model. In the course of the base measurements the retention factors (k) of the analytes were determined on three different base stationary phases; other parameters were fixed. By use of these data the k values were predicted in the cases of all theoretically combined stationary phases. These predictions resulted in numerous intermediate theoretical separations but only the optimal one was compiled and tested applying other parameters fixed as in the case of the base measurements. The overall selectivity of this separation was better than that of any individual stationary phase. SOS-LC is independent of the mechanism and the scale of separation and will be very advantageous in the case of hyphenated techniques (LC-MS and LC-NMR) due to stable mobile phase background.