A HPLC method using a modified sample preparation procedure was optimized and validated for the quantification of 10 quinolones (QNs), including marbofloxacin, ciprofloxacin, norfloxacin, lomefloxacin, danofloxacin, enrofloxacin, sarafloxacin, difloxacin, oxolinic acid, and flumequine, in swine, chicken, and shrimp tissues. In this method, only a small mass (<or=2.0 g) of sample and a relatively small volume of organic reagent (<or=4.6 mL) of a nonchlorinated extraction solvent were required. The QNs were analyzed by liquid chromatography in a single run using a gradient elution program and with a programmable fluorescence detector to obtain optimum detection wavelengths. Mean recoveries of 10 drugs from edible animal tissues at a concentration range of 1-100 ng g-1 were 72.8-106.8% with relative standard deviations below 11.2%. The limits of quantification for each QN in different muscle tissues ranged from 0.3 to 1.0 ng g-1, which were below the lowest maximum residue limits (10 ng g-1) established in many countries. The method was also applied to the measurement of QN residues in commercial muscle samples. The results showed it was rapid, simple, sensitive, and suitable for use in food surveillance programs.