Thirty-five Japanese patients with relapsing remitting multiple sclerosis (RRMS) and 11 Japanese patients with primary progressive MS (PPMS) were compared by a combined clinical, magnetic resonance imaging (MRI) and multimodality evoked potential (MEP) study. Patients with PPMS showed a more common occurrence of gait disturbance as the initial symptoms as well as a more common occurrence of cerebellar symptomatology than did those with RRMS, while spinal cord symptomatology was frequently observed in both conditions. On brain MRI, patients with PPMS had 3 times more lesions than did those with RRMS (P < 0.001, chi 2-test). The percentage of infratentorial lesions was also significantly higher in PPMS than in RRMS on MRI. Moreover, we found a significantly higher frequency of abnormal records in visual, brainstem auditory and somatosensory evoked potentials in PPMS than in RRMS. Interestingly, clinically unexpected abnormalities were significantly more common in PPMS than in RRMS throughout all modalities of MEPs. Thus, in Eastern MS, there exists a distinction between PPMS and RRMS in the MRI and MEP findings as well as in the clinical findings. Our result therefore suggest that there may be two distinct subtypes in MS.