We report here a novel high pressure liquid chromatographic (HPLC) technique for use in therapeutic monitoring of the primary amine antiarrhythmic drug mexiletine in plasma samples. Mexiletine and its structural analogue, the internal standard Ko 768, are extracted with heptane after alkalinization of the sample. The extracts are evaporated to dryness, reconstituted, and injected into a liquid chromatograph equipped with an octadecylsilane reversed phase column using an acetonitrile/acetate buffer mobile phase. Detection is by ultraviolet absorption at 254 nm. The method is linear from 0.2 to 5.0 microgram/ml; the coefficient of variation ranges from 5 to 10% within the therapeutic range. The drug is stable for at least 99 days in samples stored at -20 degrees C. Our HPLC results showed good agreement with a popular gas liquid chromatographic method (14), and there are few incidents of interference from common drugs. The method is convenient for any laboratory equipped with standard liquid chromatographic equipment and is suitable for automation.