The encapsulation of tolmetin, a nonsteroidal antiinflammatory and antirrheumatic drug, by beta-cyclodextrin (P-CD) has been analyzed from thermodynamic and structural points of view, by means of conductometric and molecular mechanics studies. Conductivity measurements of aqueous solutions of tolmetinate (TOL-) were performed as a function of beta-CD concentration, at different temperatures ranging from 15 to 40 degrees C. The stoichiometry of the complex ( 1: 1), its association constant (similar to 2000 M-1),and the ionic molar conductivities at infinite dilution of the free (lambda(DRUG)(0)) and complexed (lambda(CD:DRUG)(0)) drug were obtained from these conductivity data. A slightly negative change in enthalpy and a positive change in entropy, obtained from the dependence of K values with the temperature, reveal that both the enthalpy and the entropy favor the inclusion process. Molecular mechanics (MM) calculations, also employed to study the complexation in vacuo and in the presence of water, show that the drug prefers to penetrate into the beta-CD cavity by the wider entrance, with toluol group end first. From both MM calculations and experimental results, the hydrophobic effect and electrostatic interactions, possibly arising from the presence of intermolecular hydrogen bonds, seem to have a relevant role in the formation of the beta-CD:TOL- complex in aqueous media.