A rapid, precise, and sensitive method has been developed for the simul-taneous detemiination of tive antiepileptic drugs (carbamazcpine. phenobarbital.diphenylhydantoin, primidone, and oxcarbazepine) and six metabolites (from carbama-zepine. carbamazepin-IO. Il-epoxide; from phenobarbital. p-hydroxyphenoharbital:from primidone. 2-phenyl-2-ethylmiilonamidc; from diphenylhydantoin. 5-(/7-hydro-xyphenyl)-5-phcny!hydantoin) in human serum. Separation was achieved by meansof liquid chromatography with a diode array detector (DAD) using reverse-phaseODS-Hypersil columns (100x2.1 mm) with particle size of 5p,m, flow-rate0.6mL/niinute. column temperature 4O'"'C, wavelength: 210nm. Mobile phase was agradient consisting of solvent A: phosphate buffer pH 5.7. solvent B: McOH. Two pro-cedures were tested for the serum treatment: protein precipitation with acetonitrile andsolid-phase extraction with C|K cartridges. The best recoveries were found by means ofprotein precipitation. Solid-phase extraction gave poor recoveries for phenobarbitaland its metabolite. The results obtained are suitable in terms of preci.sion, linearity,and accuracy for the simultaneous determination of seruin levels of tlie mentioneddrugs in the usual therapieutic ranges