We have developed a simple and rapid high performance liquid chromatographic technique to determine lamotrigine concentrations in epileptic patients and validated it using external quality control material. The method has been used to monitor the lamotrigine concentration in 70 specimens from 61 patients. Only 50% of the specimens had concentrations within the proposed target range of 1 mg/L to 4 mg/L, and there was no relationship between lamotrigine concentration and age, sex, other anti-epileptic treatments, or dose, although this could in part be explained by concomitant anti-epileptic therapy. We suggest that lamotrigine should be monitored therapeutically in order to assess its efficacy and audit its use as an anti-epileptic treatment, especially with the introduction of this relatively new drug as monotherapy.