MM2 calculations correctly reproduce both the X-ray geometry of γ-cyclodextrin and its ability to distinguish between various alkyl substituents on a substrate, leading to different host-guest complexes. The theoretical results show a clear correlation with experiments. Solvent effects seem to be unimportant for the complexation preference within a series of compounds. The inclusion process is mainly, but not exclusively, controlled by van der Waals attractions. © 1994, American Chemical Society. All rights reserved.