Experimental and theoretical evidence is provided that indicates the presence of inclusion complexes in the gas phase when cyclodextrin and amino acid mixtures are electrosprayed into a Fourier transform mass spectrometer. A guest exchange reaction that is enantiospecific is used to probe the structure of the gas-phase complex. Chiral selectivity is affected by both the size of the guest and the size of the cavity. These observations are based on a selected number of amino acids with various hosts. The experimental results are supported by molecular dynamics calculations. We further conclude that rather than nonspecific complexes, amino acid-cyclodextrin complexes produced in solution maintain the included structure even in the gas phase.