A simple and reproducible method for the simultaneous determination of the nonsteroidal anti-inflammatory agent, furprofen, and the quinolone antimicrobial agent, rufloxacin, in human plasma is described. It involves a two-step liquid-liquid extraction and a separation using an LC-SAX column with ultraviolet detection at 280 nm. Fenbufen is used as the internal standard. Within-day and between-day coefficients of variation are less than 6%. The lower limits of detection are 0.05 and 0.03 micrograms/mL for furprofen and rufloxacin, respectively. The method is suitable for pharmacological, toxicological, and pharmacokinetic studies of furprofen and rufloxacin.