The quinolone antimicrobials contain one acidic and one basic functional group and at physiological pH they exist as a mixture of the neutral and zwitterionic forms. The ratio of the neutral to zwitterionic species for a given compound is important because it is likely to determine the distribution properties of the drug in vivo. The present study was conducted to determine the relationship between the dissociation constants of the quinolones and their chemical structures. Regression analyses indicated that the apparent pKa value associated with the carboxylic acid function was influenced by the number of fluorines in the molecule, while the pKa value associated with the piperazinyl nitrogen was influenced mainly by the presence of an N-methyl substituent.