An automated high-performance liquid chromatographic column-switching system is presented for the analysis of antiepileptic drugs in serum. Initial results show that a reversed-phase extraction column works best overall when fitted with screens versus frits, and when packed with porous 30-micron particles as opposed to a pellicular packing of similar size or with smaller porous particles. The continuous analysis of primidone for over 2000 serum samples is achieved at a rate of twelve samples per hour with a single analytical column. An analogous boxcar high-performance liquid chromatographic system is also assembled and used to analyze two of four injected antiepileptic drugs at a rate of 40 samples per hour. For 1000 of these analyses, the coefficient of variation is 1% without an internal standard.