We evaluated the clinical and laboratory features of the optic-spinal form of multiple sclerosis (OSMS) with no brain lesions on repeated MRI--termed pure OSMS. By reviewing the medical records of 118 Japanese clinically definite multiple sclerosis patients seen between 1988-1999, we found 10 patients (8.5%), nine of whom were women, with only relapsing optic neuritis (ON) and myelitis (MY) clinically and consistently normal brain MRI during follow-ups of >or=5 years. Three patients suffered severe ON and MY, but the other seven had mild disease (six were graded 1 in the Disability Status Scale). Despite frequent relapses, mild pure OSMS was characterized by younger onset and mild spinal symptoms as in 'benign' classical multiple sclerosis (CMS). MRI often revealed multiple cervico-thoracic cord lesions of variable lengths. Oligoclonal IgG bands (OB) were negative in all cases. HLA-DPB1*0501, whose association with OSMS has been reported, was positive only in six patients (including three patients with severe pure OSMS). Four patients with DRB1*1501-DQB1*0602, to which CMS is closely linked, had mild disease. Though pure OSMS was heterogeneous with regard to clinical severity and human leukocyte antigen (HLA) class II alleles, this form of multiple sclerosis was characterized by a definite female preponderance and negative OB that distinguished it from CMS.