Tricyclic antidepressant poisoning is one of the most common causes of serious intoxication. Here, we report a 2-year-old girl with severe amitriptyline (70 mg/kg) intoxication. She was in comatose, had generalized tonic clonic seizure, ventricular tachycardia, and wide QRS complexes. Although she did not respond to classical therapies, very good clinical response to plasmapheresis was obtained and she developed no complications. Thus, plasmapheresis may be an effective treatment modality in poisoning with drugs, which bind to plasma proteins with high affinity. J. Clin. Apheresis, 2009. © 2009 Wiley-Liss, Inc.