Postmortem examination of 21 patients showed a vacuolar myelopathy resembling that associated with the acquired immunodeficiency syndrome. Underlying diseases included six cases of leukemia or lymphoma, five of carcinoma, three of systemic lupus erythematosus, two of chronic lung disease, and one each of cadaveric renal transplant, cirrhosis, diabetes, hemophagocytic syndrome, and viral encephalitis. Fourteen patients were on long-term steroid therapy and 10 of these also had immunosuppressive chemotherapy. No patient had the acquired immunodeficiency syndrome, although one received blood transfusions in 1978. Signs and symptoms consistent with myelopathy included paraparesis in seven patients, ataxia in one, and bilateral extensor plantar reflexes in one. Microscopic examination showed vacuolation in spinal cord white matter primarily located in posterior and lateral columns. Lipid-laden macrophages and axonal changes were proportional to the severity of the vacuolation, which was severe in five patients, moderate in 10, and mild in six. Eight patients had coexistent viral diseases elsewhere in the central nervous system, but viral-associated antigens or genomic material was not found in regions of vacuolated spinal cord white matter. Although the etiology of these myelopathies is unknown, their association with immune suppression and coexistent viral infection of the central nervous system suggests that an opportunistic viral infection may be important.