Purpose: To report that acute lamotrigine poisoning may result in severe encephalopathy. Methods: A 55-year-old woman became stuporous after overdose with lamotrigine (LTG) and valproic acid (VPA) tablets. Evaluation revealed elevated serum LTG levels and no other etiology for encephalopathy. Results: LTG was withheld, and the patient experienced a complete recovery in conjunction with reduced serum levels. Conclusions: LTG overdose may result in a severe but reversible encephalopathy, a previously undescribed phenomenon. LTG toxicity should be considered in patients taking this drug who have depressed mental status.