With the aim of learning about the solubility characteristics of retentive and mobile phases often encountered in reversed-phase liquid chromatography (RPLC) and to examine the driving forces for retention, configurational-bias Monte Carlo simulations in the Gibbs ensemble were carried out for systems consisting of three phases: an n-hexadecane retentive phase (serving as a model of the hydrophobic RPLC stationary phase), a mobile phase with varying water-acetonitrile or water-methanol composition, and a helium vapor phase (serving as an ideal gas reference state). Gibbs free energies of transfer between each of these phases were computed for a series of small alkane and alcohol solutes and from these the methylene and hydroxyl increments were determined. The results indicate that both nonpolar and polar solutes have favorable interactions with both the mobile and stationary phase thus showing that neither the solvophobic theory nor lipophilic theory alone can explain the driving forces for retention in RPLC. In addition, an analysis of the solvation environments of methylene and hydroxyl groups in the mobile and stationary phases was carried out. The methylene group is shown to be preferentially solvated by the organic component of the aqueous-organic mixture, however, clustering of the organic solvent molecules in the absence of the solute was not observed. For the hydroxyl group, hydrogen bonding was shown to be important in both the mobile and stationary phases. (C) 2009 Elsevier B.V. All rights reserved.