A second-derivative spectrophotometric method for the determination of naproxen in the absence or presence of its 6-desmethyl metabolite in human plasma is described. The method consists of direct extraction of the non-ionized form of the drug with pure diethyl ether and determination of the naproxen by measuring the peak amplitude (mm) in the second-order derivative spectrum at a wavelength of 328.2 nm. The efficiency of the extraction procedure expressed by the absolute recovery was 94.6 +/- 0.7% (mean +/- s) for the concentration range tested, and the limit of quantification attained according to the IUPAC definition was 2.42 mg l-1. The linear dynamic range for naproxen was 5.0-100.0 mg l-1, the correlation coefficient for the calibration graphs was excellent, r = 0.99993 (n = 6), the precision (Sr) was better than 4.58% and the accuracy was satisfactory (Er < 2.32%). The results obtained by the proposed method were in good agreement with those found by an HPLC method.