The chromatographic behavior of aprotic neutral molecules in Ion Interaction Chromatography (IIC) was investigated both theoretically and experimentally on a styrene-divinylbenzene based C18stationary phase. The chemical modification of the stationary phase in the presence of Ion Interaction Reagent (IIR) in the eluent, and adsorption competition between tested analytes and IIR for inner layer sites are theoretically shown to change the partition coefficient for neutral molecules.