Titration calorimetry was used to measure equilibrium constants and standard molar enthalpies for the reactions of phenethylamine, ephedrines, and related substances with alpha- and beta-cyclodextrin. Changes in the chemical shifts Delta delta of both the ligand and cyclodextrin protons were measured with NMR. The thermodynamic results have been examined in terms of structural features of the ligand that affect these interactions such as the separation of the charge at an amino group and the aromatic ring, steric effects, the presence of additional functional groups (amino, hydroxy, methoxy, and methyl) attached to the aromatic ring, the presence and location of hydroxy group(s) on the ligand, changes in the chirality of the ligand, and the flexibility of the organic molecules attached to the aromatic ring. It was found that the values of thermodynamic quantities for these reactions in phosphate and acetate buffers were different. This difference is attributable to the presence of a hydrophobic alkyl group in the neutral acetic acid molecule and its interaction with the cyclodextrins. Also, there are significant differences in the thermodynamic quantities for the reactions of the chiral isomers of ephedrine and pseudoephedrine in their reactions with beta-cyclodextrin.