Alteration of monoamine levels by some antiepileptic drugs (AEDs) was elucidated in this study. Lamotrigine (LTG) is a new AED, acting the sodium-channels. LTG was given as add-on therapy to 16 patients aged 4.5-18 yrs with intractable epilepsy and comedicated with carbamazepine or valproate. An equal group of epileptics with comparable clinical characteristics and treatment served as control. Plasma and urinary (24 h-samples) serotonin and 5-HIAA were determined before onset of LTG therapy and after 2-3 months. HPLC and electrochemical detection was used for the determination of serotonin (5-HT) and 5-hydroxy indoleacetic acid (5-HIAA). No significant effect of LTG on both urinary 5-HT and 5-HIAA levels was found, whereas plasma 5-HT concentrations significantly decreased in comparison with levels before LTG starting and relevant values in controls. This findings was noted in 7/16 children with favourable response to LTG. Increased serotonin catabolism may be result of LTG action.