We have modified and validated a capillary GC-MS method reported by Kadowaki et al. [J. Chromatogr., 308 (1984) 329] for the determination of diclofenac in human plasma by using heptane rather than benzene as an extraction agent. In addition, acetone was added to the samples as a deproteination agent which increased the recovery of diclofenac. These revised processes allowed clean extraction and near-quantitative recovery of analyte (> 95%). Separation was achieved on an HP-1 column with helium as carrier gas. The parent ion peaks of diclofenac (m/z 277) and the internal standard, 4'-methoxydiclofenac (m/z 307), were monitored by a mass-selective detector using the selected-ion monitoring mode. The linear range for the routine assay was from 5 to 2000 ng/ml. The detection and lower quantifiable limits were 0.2 and 1 ng/ml, respectively, with no interference from plasma. The within-day and between-day coefficients of variation for high and medium concentrations were less than 5% and were less than 13% for low concentrations (10 ng/ml). This GC-MS assay method has been used for pharmacokinetic and drug interaction studies in humans.