Abstract An adsorption study of binary polar solvent mixtures by hydrocarbon-bonded chromatographic silica is presented which emphasizes the role of interfacial thermodynamics in the interpretation of retention volumes in reversed-phase liquid—solid chromatography. The composite adsorption isotherms of the three binary systems formed by acetonitrile (A), methanol (M) and water (W) on a C 18-modified silica surface were determined over the entire composition range by frontal analysis chromatography, and the thermodynamic consistency of these results was tested. In addition, the enthalpies of displacement, Δ ji H, of solvent i by solute j at the surface of two alkyl-modified porous-layer-bead materials was measured for the same liquid systems by flow calorimetry. The systems W + A and W + M exhibit S-shaped surface excess isotherms with negative (exothermic) Δ ji H values at both ends of the composition range. The molar enthalpy of displacement, Δ ji h, (defined in terms of a simple surface phase model) for A and M from dilute aqueous solutions is about −7 kJ/mol, and is attributed to hydrophobic interactions with the surface alkyl chains. Adsorption of W from dilute solutions in A yields much greater Δ ji h values which are attributed to hydrogen-bond interactions of water with free surface silanol groups. In the system W + A (which exhibits large positive deviations from ideal mixing behaviour) multi-layer adsorption of A occurs on the non-polar surface at compositions near the maximum of the surface excess isotherm.