Drug poisoning as a result of tricyclic antidepressant overdose is frequently encountered in emergency departments and is a significant cause of mortality and morbidity. The usual route of administration is oral. Here we report the case of a 42-year-old man with a history of depression who had taken a large overdose of amitriptyline by the rectal route. This case highlights the management difficulties that arose as a result of rectal administration of the drug and possible ways in which treatment should differ from that of an oral overdose.