The alpha-ciclodextrin (alpha-CD) consist of six glucopyranose units. The crystalline form I of alpha-CD is obtained in the solid state as the hexahydrate structure (alpha-CD . 6H(2)O) containing two water molecules inside and four outside the cavity. In this Letter, we report a quantum chemical study of the formation of the alpha-cyclodextrin hexahydrate using the semiempirical PM3 method and Density Functional Theory (BLYP/6-31G(d,p) calculation). Distinct chemical processes are considered for the calculation of the thermodynamic properties. We found a good agreement with experimental data for entropy, enthalpy and Gibbs free energy, which add support to the theoretical approach we used. (C) 2004 Elsevier B.V. All rights reserved.