A new approach based on a selective charge transfer reaction with alizarin red S is described for the simultaneous determination of azithromycin and levofloxacin in their binary mixtures using an absorption-factor spectrophotometric method. Native absorbance was used for the determination for levofloxacin, while a charge transfer complexation of alizarin red S served as the basis for the quantitation of azithromycin. The reaction of azithromycin with alizarin red S was possible in methanol under neutral conditions within 15 min at 25 degrees C. The conditions were suitably optimized for selective complexation of azithromycin with minimal interference from levofloxacin. The calibration curve was linear over the concentration range of 4.0-20 mu g mL(-1) for azithromycin and levofloxacin and the correlation coefficients of the regression equations were consistently greater than 0.9970 for both the drugs. The limit of detection was 1.07 mu g mL(-1) for azithromycin and 0.84 mu g mL(-1) for levofloxacin. The developed method was highly reproducible with precision (RSD%) values in the range of 0.54%-0.95% for both the drugs. The method was successfully applied for the simultaneous determination of these antibacterial drugs from their synthetic mixtures and pharmaceutical formulations with no interference from excipients.