The relative stability of zwitterionic and uncharged neutral forms of the fluoroquinolone antibiotic levofloxacin has been investigated using quantum mechanical calculations at the B3LYP/6-31+G* level. Solvent effects have been incorporated using continuum and discrete-continuum models. The zwitterion is slightly more stable than the uncharged form in water where hydrogen bonds are shown to play a key role. Energy transfer from water to an apolar medium has been computed as an attempt to estimate the energy involved in crossing a lipid bilayer. The obtained value (-2.9 kcal/mol) is consistent with the intermediate lipophilicity experimentally measured for this drug. (C) 2007 Elsevier B.V. All rights reserved.