In contrast with temperature, pressure is often overlooked as an important parameter in condensed phases primarily due to minimal perturbations in bulk properties. Molecular interactions, however, have been demonstrated to be significantly altered by relatively modest pressure (<500 bar) in a number of biologically based studies. In this article, we examine the fundamental role of these pressure perturbations on enantiomeric complexation with beta-cyclodextrin. Widely utilized for enantioselective interactions, beta-cyclodextrin provides a hard-binding site with a pressure-invariant structure. Using this rigid molecule and enantiomers of warfarin, pressure-induced perturbations in complexation equilibria may be used to determine the change in partial molar volume upon complexation. Complexation measurements by liquid chromatography demonstrate a significant decrease in solute binding for both enantiomers under controlled-pressure conditions (P-av < 300 bar). On the basis of these measurements, both enantiomers are shown to exhibit significant changes in molar volume upon complexation (Delta V-comp = +17+/-5.1 cm(3)/mol; Delta V-comp = +16+/-5.0 cm(3)/mol). Moreover, pressure-induced perturbations in chiral selectivity yield a small but significant difference in the change in partial molar volume of the solvated complexes, Delta(Delta V-comp) = 1.0+/-0.50 cm(3)/mol. For enantiomers, which are expected to have identical molar volumes in solution, this difference in Delta V-comp arises primarily from the partial molar volumes of the solvated complexes. These differences in the solvation environment between enantiomers are central to chiral recognition, and further study will be required to elucidate mechanistic distinctions. Generally utilized as a separation technique, liquid chromatography is demonstrated here as a powerful tool for the sensitive determination of pressure-induced perturbations in chiral complexation.