An increased prevalence of vitamin B12 deficiency has been reported in patients infected by the human immunodeficiency virus (HIV). We report an unexpectedly high prevalence (20%) of such abnormal vitamin B12 metabolism in a population of HIV-infected patients referred for neurological evaluation. This abnormality was associated with both peripheral neuropathy and myelopathy. A majority of those treated with cyanocobalamin had a therapeutic response. Selected neuropathological results suggest a relationship between vitamin B12 deficiency and vacuolar myelopathy. Vitamin B12 deficiency may be a frequent and treatable cause of neurological dysfunction in patients with HIV infection.