To see the quantitative relationship between the structures of the C-7 substituted quinolones and their antibacterial activities, theoretical parameters such as the molecular van der Waals volume, surface area and some electrostatic parameters based on the molecular electrostatic potential, which represent lipophilicity, and some quantum mechanical parameters are introduced as descriptors. The sixteen substituted quinolone derivatives and twenty bacteria are used for the study. It is found that the QSARs of C-7 substituted quinolones are obtained for eleven bacteria and our descriptors are more useful for Gram positive organisms than negative ones. It is also shown that molecular surface area (or molecular Waals volume) of the C-7 substituent and net charge of C-7 atom of the quinolones are the descriptors of utmost importance.