The interaction of 5,11,17,23-tetra-tert-butyl [25,26,27,28-tetrakis(2-pyridylmethyl)oxy]calix(4)arene 1a with alkali-metal cations in dipolar aprotic media (acetonitrile and benzonitrile) has been investigated. ¹H NMR experiments were carried out by adding to the ligand an excess amount of the appropriate metal cation (Li⁺, Na⁺, K⁺) in CD₃CN at 298 K. Measurements were taken at different time intervals ranging from 30 min to 10 days. It was found that the kinetics of the process in this solvent is fast. Conductance measurements demonstrated that 1:1 metal cation:ligand stoichiometries are found with these cations in these solvents. Thermodynamic parameters of complexation for this ligand and alkali-metal cations in acetonitrile and in benzonitrile at 298.15 K were derived from titration microcalorimetry. Stability constants were also determined by the competitive potentiometric method using silver electrodes. Excellent agreement is found between the data derived from calorimetry and those derived by potentiometry. The highest stability is found for lithium with this ligand. The results are compared with data previously reported for systems involving a calix(4)arene ester derivative and these cations in the same solvents. The implications of stability constant data on the selective behaviour of this ligand for metal cations in these solvents are discussed. It is shown that this ligand in these solvents is able to discriminate between the smaller cations (Li⁺ and Na⁺) and the larger ones (K⁺ and Rb⁺). The sodium perchlorate complex of 1a was synthesised and the molecular structure of this complex has been determined from X-ray diffraction data. The substance crystallises in the tetragonal group P4cc with a=21.791(2), c=26.958(3) Å and z=8. There are three different complexes in the lattice, two sited on fourfold axes and a third one on a twofold axis. All ligands exhibit a ‘cone’ conformation and the Na⁺ ion is encapsulated in their hydrophilic pockets with an acetonitrile molecule filling their hydrophobic cavities. Based on ¹H NMR, conductimetric, microcalorimetric and X-ray diffraction studies final conclusions are given.