The synthesis and characterization (H-1 NMR) of two new lower rim calix(4)arene derivatives containing mixed pendent arms, namely, 5,11,17,23-tetrakis(1,1-dimethylethyl)-25,27-bis[2-(methylthio)ethoxy]-26,28-bis[(pyrid-2-ylmethyl)oxy]calix(4)arene (1) and 5,11,17,23-tetrakis(1,1-dimethylethyl)-25,27-bis[2-(methylthio)ethoxy]-26,28-bis[(pyrid-3-ylmethyl.)oxy]calix(4)arene (2). are reported. Transfer thermodynamic parameters of these ligands to various solvents show that these macrocycles undergo selective solvation in nonaqueous media. As far as the alkali-metal cations are concerned, 1H NMR measurements reflect that 1 in CD3CN discriminates against the largest cations (K+, Rb+, and Cs+) but interacts with Li+ and Na+. These interactions appears to be more pronounced with the pendent arms containing the pyridyl ring (through the ethereal oxygens and nitrogen donor atoms) than with those containing the (methylthio)ethoxy arms (only ethereal oxygens are involved). No interaction takes place between its isomer 2 and alkali-metal cations in CD3CN. The complexation of the lithium and the sodium complexes was established through conductometric titrations. In all cases investigated 1: 1 (ligand: metal cation) complexes are formed in acetonitrile and in benzonitrile. On the basis of the semiquantitative information provided by conductance measurements regarding the strength of complexation of I and the sodium cation, the sodium monoacetonitrile complex of I was isolated and its structure determined by X-ray diffraction methods. Thus, the cation was found in the hydrophilic cavity while the hydrophobic cavity hosts a molecule of acetonitrile. The crystallographic results confirm the key role played in the chelating process by the ethereal oxygens and the pyridyl nitrogens at the 2-position in the terminal pyridyl groups, as found in solution. The thermodynamics of complexation of I and alkali-metal cations (Li+ and Na+) in two dipolar aprotic solvents is interpreted in terms of the solution thermodynamics of the reactants and the product. It is the availability of these data that allows interpreting the different enthalpic and entropic contributions resulting from cation, solvent, and ligand effects. Final conclusions are given.