An isocratic high-pressure liquid chromatographic method for the determination of naproxen and its desmethyl metabolite in human plasma is presented. A reversed-phase octadecylsilane column was utilized with a mobile phase consisting of 55% methanol and 45% 0.10 M acetate buffer, pH 5.0. A spectrofluorometric detector with an excitation wavelength of 253 nm and a band pass filter provided high sensitivity with no interference from normal plasma constituents. The reproducibility and precision of the method were shown by analysis of spiked samples containing 2.5-70 micrograms/ml of plasma.