We describe a method for the simultaneous determination of valproic acid with four other antiepileptic drugs (phenobarbital, phenytoin, carbamazepine, and primidone) in plasma by high-performance liquid chromatography. These drugs are extracted from plasma by adding a small volume of acetonitrile following saturation with ammonium sulphate. An aliquot of the extract is then injected on a reversed-phase column with a methanol-water mobile phase. The total time required for the whole analytical process including the plasma pretreatment and chromatography is approximately 20 min. The assay method is simple, rapid, reproducible and specific, and considered, therefore, suitable for both emergency and routine uses in monitoring these antiepileptic drugs simultaneously.