Inclusion modes in complexes with α- and β-cyclodextrins in water have been investigated by NMR spectroscopy at 400 or 500 MHz, and compared with structures obtained by computer-aided molecular modelling and with calorimetric data. The NOEs observed on o- and m-aryl protons upon irradiation of either H3 or H5 inside the CD cavity indicate for all phenols an inclusion mode with the hydroxy group at the wide cavity end, and an increasingly deep immersion for phenol or phenolate with iodine compared with this nitro group, as para-substituent. This is found to be in line with the complexation-induced NMR shifts. Adamantane-1-carboxylate is indicated by distinct NOEs to be fully immersed into the β-CD cavity; the corresponding complex with α-CD shows contact only at the wider rim and a tilted conformation which allows formation of a hydrogen bond between the guest COO^– and the 2-OH group of the CD. The same conformation is found by CHARMm calculations, including simulations in a water box. The results, together with some ΔG^o values derived from NMR titrations, are in line with data from calorimetric studies. These show for complexes with tight fit (in α-CD) large enthalpies of up to 43 kJ mol^–1 as the predominating driving force against sizeable entropy disadvantages (TΔS^o⩽–24 kJ mol^–1), particularly for guest molecules of higher electron density and/or polarizibility. These observations point to predominating dispersive interactions. In contrast, inclusion in the wider β-CD cavity suffers less from entropy disadvantage (TΔS^o⩽–11 kJ mol-¹); the binding, however, is still dominated by ΔH^o, pointing to predominant cohesive and not entropic hydrophobic forces.