The zwitterionic antihistamine cetirizine and its parent drug hydroxyzine as reference compound were examined for their 3D structures and dynamics. After attributing, by NMR spectroscopy, the two basic pK(a) values. the most common conformations for each electrical species were determined by molecular-dynamics simulations and confirmed by NMR measurements. For cetirizine, the results demonstrate that the zwitterion, which is the predominant species at physiological pH, exists as folded conformers able to partly mask polar groups. Extended and folded conformers of similar energy were also found for neutral hydroxyzine. whereas its monocationic species displayed folded conformers stabilized by intramolecular H-bonds. These findings are in lull agreement with previous results on the lipophilicity behavior of cetirizine in isotropic solvent systems and, taken together, could explain the favorable pharmacokinetic properties of the drug