Transverse myelitis has been cited as a rare and unusual complication of systemic lupus erythematosus (SLE). A review of the literature reveals only 10 cases of transverse myelitis as the initial presentation of SLE, and only one with reported benefits from antimalarial therapy. The case of a 30-year-old woman is reviewed. She presented to the emergency room with complaints of hypogastric and low back pain. The ensuing course was one of frank urinary retention and rapidly progressing quadriparesis. Magnetic resonance imaging of the spine revealed marked edema of the cervical and thoracic spine. A diagnosis of SLE was based on positive antinuclear antibodies and leukopenia. The patient was treated with high dose methylprednisolone, plasmapheresis and pulse cyclophosphamide for 3 months. Subsequently, treatment was begun with hydroxychloroquine, and significant improvement in her neurologic and functional status was achieved after 1 month of therapy. Ten months after her onset of symptoms, the patient suffered an acute exacerbation of paraparesis and urinary retention. Again, she improved clinically after high dose methylprednisolone and pulse cyclophosphamide for 1 month. Hydroxychloroquine was continued throughout the duration of therapy.