A quantitative method has been developed for valproic acid and twelve of its metabolites using capillary gas chromatography--mass spectrometry with selected-ion monitoring. The method is applicable to serum or urine and all metabolites are measured in a single run. Ions selected for quantitative purposes were the characteristic (M-57)+ ions of the tert.-butyldimethylsilyl (tBDMS) derivatives. The 4-hydroxyvalproic acid was measured as the gamma-lactone. Calibration curves were found to be linear and the sensitivities in the order of 0.1 microgram/ml. Patient data are presented. A comparison of tBDMS and trimethylsilyl (TMS) derivatives showed that tBDMS gave superior sensitivity for the unsaturated metabolites and a shorter analysis time. Mixed tBDMS-TMS derivatives were also investigated.