A 57-year-old woman who had severe opticospinal multiple sclerosis (OSMS) was admitted to our hospital. She had presented with visual loss and gait disturbance at the age of 48, and had since experienced more than 10 relapses and been hospitalized 9 times. Interferon beta-lb treatment (8,000,000 units on alternate days) had been started at her last admission. Prior to the present admission, she had developed left visual loss and gait difficulty after headache lasting a few days. Cerebrospinal fluid showed elevation of cell count (322/mm3), protein (130 mg/dl), and myelin basic protein (462 pg/ml; normal, <102 pg/ml). On examination, she exhibited decreased left visual acuity, paraplegia, ataxia of the right upper extremity, and sensory disturbance, particularly in the lower extremities. Bowel and bladder disturbances were also evident Laboratory testing showed lymphocytopenia (420/microl), compared to a white cell count of 1700/microl just before initiation of interferon beta-lb1therapy. MRI revealed a new lesion in the cerebellum in addition to small T2-hyperintense lesions in the white matter of the brain;these had been noted previously. Interferon beta-1b therapy was ceased and she was treated using methylprednisolone pulse therapy. After the abnormal findings resolved, however, interferon beta-lb1therapy was restarted. Three months after, she exhibited right hemiparesis without facial palsy concurrent with lymphocytopenia. MRI showed T2-hyperintense lesions in the periventricular white matter, left cerebral peduncle, bilateral middle cerebellar peduncles, and right cerebellar hemisphere. We reduced the doses of interferon beta-lb1immediately. Thereafter, she did not have relapse for 29 months, but her EDSS (expanded disability status scale) has not recovered. Although interferon beta-lb1has been recognized as an effective drug for decreasing the relapse rate and severity of both secondary progressive MS and relapsing-remitting MS, the present case showed the possibility of interferon beta-1b being associated with phenotype change from OSMS to conventional MS (CMS).