The H/D and D/H exchange rates of hydroxy groups in crystalline α-cyclodextrin (CD) exposed to H 2 O and D 2 O vapour, respectively, have been studied by monitoring the relative integrated Raman intensities of the O–H and O–D stretching bands. The time-dependent Raman intensities suggest a fast diffusion-controlled H 2 O/D 2 O equilibrium process in shorter times, followed by a much slower H/D exchange for the longer times. The deuteriation process is found to be ca. 10 times slower than the reverse process, in excellent agreement with the expected isotopic effect in an exchange mechanism whose rate-determining step involves the cleavage of a O–H(–D) bond of a water molecule. The slow H/D exchange rate observed for α-CD hexahydrate in comparison with the β-CD dodecahydrate is explained by its structural rigidity, also evident from the discrete bands observed in the O–H and O–D stretching region. This structural rigidity is no longer present in the inclusion compounds of α-CD with an aromatic guest, which exhibit an H/D exchange rate much faster than the pure α-CD hexahydrate.