A HPLC method for the determination of mexiletine in human plasma and serum is described. Serum or plasma after addition of mexiletine and internal standard was extracted with diisopropyl ether. The extract was then evaporated and dissolved in the mobile phase. An aliquot of the solution was chromatographed on a reversed-phase C8 column. The peaks were detected by UV (214 nm) at room temperature. The limit of detection of mexiletine was approximately 0.02 mg/l of plasma or serum. The validity of the method is discussed and compared with other methods.