A relatively rapid, inexpensive, sensitive and stereospecific gas chromatographic-mass spectrometric method was developed for the quantification of S(+) and R(-)-ibuprofen in human plasma. This method uses a commercially available internal standard and has no interference from endogenous substances nor metabolites. The method involves derivatization of ibuprofen enantiomers with optically active R(-)-2,2,2-trifluoro-1-(9-anthryl)ethanol using oxalyl chloride as the coupling reagent. The subsequently formed diastereoisomers are separated by gas chromatography and analysed by mass spectrometry using selected-ion monitoring. The assay is successfully applied to a pharmacokinetic study. The simplicity, sensitivity and precision of the method make it convenient for the quantification of ibuprofen enantiomers in biological samples.