Intramuscular injection of benzathine-benzylpenicillin can cause acute transverse myelopathy. The purpose of this report is to describe a case of acute transverse myelopathy observed after injection of benzathine-benzylpenicillin in a 38-year-old man. The patient who was married and had a history of eczema was admitted to the Department of Neurology of the Fann University Teaching Hospital in 2006. All laboratory findings were normal except high serum immunoglobulin E level. An immunoallergic reaction involving inflammatory transverse myelopathy secondary to vasculitis was proposed as the most likely underlying mechanism. Treatment with corticosteroid and physiotherapy led to a favorable outcome. Health personnel should know the indications for use of benzathine-benzylpenicillin and be aware of the possible medullary complications.