Two isomeric structures of meso-tetramethyltetrakis(3-hydroxyphenyl)calix[4]pyrrole, 4-alpha alpha beta beta and 4-alpha beta alpha beta, have been isolated and characterized by H-1 NMR in different solvents (CD3CN, CD3OD, and DMSO-d(6)) at 298 K. Standard Gibbs energies of solution derived from solubility data in various solvents were used to calculate the transfer Gibbs energy, Delta(t)G degrees, of these ligands using acetonitrile as the reference solvent. These results are consistent with the 1H NMR studies in different media that show chemical shift changes observed in the resonances of the NH and the OH protons of these ligands. Solvate formation was observed when these isomers were exposed to saturated atmosphere of N,N-dimethylformamide, dimethyl sulfoxide and propylene carbonate. Anion interaction involving 4-alpha alpha beta beta and 4-alpha beta alpha beta was investigated by H-1 NMR in CD3-CN while the complex composition was assessed through conductance measurements. Significant differences are observed in the affinity of these ligands for anions as well as in the composition of the fluoride complexes. Thus 4-alpha alpha beta beta shows selectivity for H2PO4- in acetonitrile while its isomer 4-alpha beta alpha beta is selective for the fluoride anion. Again the complex composition is altered for the fluoride anion when complexed with 4-alpha alpha beta beta in acetonitrile (1:1 complex) relative to 4-alpha alpha beta beta in the same solvent. The latter isomer shows an enhanced hosting ability for this anion. Thus two anions are taken up per unit of ligand. The thermodynamics of complexation of H2PO4- and these ligands in acetonitrile is discussed, and the results are compared with those involving calix[4]pyrrole and this anion in this solvent. It is shown that the isomers interact with two H(2)PO4(-) anions while one calix[4]pyrrole unit interacts with this anion. This paper demonstrates for the first time that the enthalpy parameter may be a suitable reporter of the number of hydrogen bonds formed when calix[4]pyrrole and its derivatives interact with the dihydrogen phosphate anion in acetonitrile. In moving from acetonitrile to N,N-dimethylformamide, 4-alpha alpha beta beta is unable to enter complexation with most anions, except fluoride, with which the formation of a 1:2 (ligand:anion) complex is demonstrated. The rather versatile behavior of these receptors for anions is explained on the basis of 1H NMR evidence and solvation effects. These investigations highlight the importance of the medium effect on the stability of the complex and reflect the inherent nature of the solvent and its highly significant involvement in the complexation process.