IgG from individual cerebrospinal fluid (CSF) and sera from patients with multiple sclerosis and from controls was isolated by protein A-Sepharose column chromatography and tested in the tadpole optic nerve system for myelinotoxic activity. Oligoclonal IgG was present in all multiple sclerosis CSF specimens used. All IgG preparations yielded optic nerve myelin lesions, indicating that IgG has myelinotoxic activity. Significantly higher numbers of myelin lesions were obtained with IgG prepared from multiple sclerosis CSF compared to control CSF IgG.