The most common disease of the spinal cord in human immunodeficiency virus (HIV) infection is vacuolar myelopathy. Pathology studies have demonstrated that vacuolization in the thoracic spinal cord is present in more than a third of patients with AIDS. The disease, however, manifests clinically only when the vacuolization in the spinal cord has become severe, with prominent myelin loss in the lateral and posterior columns. Vacuolar myelopathy presents usually with slowly progressing spastic paraparesis, accompanied by loss of vibratory and position sense and urinary frequency and urgency. In males, erectile dysfunction can be an early manifestation of the disease. The pathogenesis of vacuolar myelopathy is unknown but may be related to abnormal trans-methylation mechanisms induced by the HIV virus and cytokines. There is no known treatment for the disease, although therapy with methylating agents is being investigated. There are other rarer causes of spinal cord disease in AIDS, including a number of infectious myelitis and neoplastic and vascular myelopathies.