Abstract This third part on the PREOPT-W program description deals with program modules that construct the simulation model (departing from the available operational, priming, information and control data) and those devoted to isocratic separations optimization. Special attention has been paid to Chromatographic response functions that can be used in HPLC optimization. Several of these functions are at the choice of the PREOPT-W user. Relative merits and drawbacks, as well as cautions in the practical use of these response functions inside PREOPT-W are now discussed in some detail. Three examples using real data covering rather different Chromatographic problems are used along this part and, once introduced, will be used also in Part IV of this series.