A reverse-phase high-performance liquid chromatographic (HPLC) method for the measurement of lamotrigine (LTG) simultaneously with phenobarbitone (PB), phenytoin (PHT), and carbamazepine (CBZ) is described using hexobarbital as the internal standard. The method uses the chromophore at 307 nm to detect LTG in the presence of interfering CBZ-10,11-epoxide detected at 220 nm, the wavelength used to measure the other drugs. This method requires < 10 min/sample for completion. Simultaneous monitoring of the chromatographs at 220 and 310 nm with a simple calculation allows LTG to be measured virtually identically to a routine method for monitoring of the other anticonvulsants. Between-batch precisions for LTG at 2 and 6 mg/L were < 5%. Accuracy of LTG estimation was assessed by comparison with known values of samples supplied by an external quality assessment scheme.