We have evaluated the hydroxyl group–solvent and carbonyl group–solvent specific interactions by using mostly an Alltima C 18 stationary phase and subsidiarily squalane-adsorbed C 18 phase, and by measuring the retention data of carefully selected solutes in 60:40, 70:30, 80:20 and 90:10 (%, v/v) methanol–water eluents at 25, 30, 35, 40, 45 and 50°C. The selected solutes are four positional isomers of phenylbutanol, 5-phenyl-1-pentanol, three positional isomers of alkylarylketone derived from butylbenzene, and 1-phenyl-2-hexanone. The magnitudes of carbonyl group–solvent specific interaction enthalpies are larger than those of hydroxyl group–solvent specific interaction enthalpies in general. We observed clear discrepancies in functional group–solvent specific interactions among positional isomers. The spatial accessibility of the functional group by the solvent molecules seems to govern the strength of interaction. The relationships between molecular structures and functional group accessibilities have been discussed. The specific functional group–mobile phase interactions obtained by the Alltima C 18 stationary phase were systematically different from those obtained by the squalane-impregnated C 18 stationary phase, which may be due to structural differences between the two phases.