Although cyclophosphamide pulse therapy has been reported to be beneficial for patients with chronic progressive multiple sclerosis for whom other treatment modalities are not expected to improve outcome, the experience with Japanese patients has not been shown in the literature. The reason appears due, in part, to the small size of this group and to the side effects inherent to such a large dose immunosuppressive regimen. Here, we report on 3 cases with chronic progressive multiple sclerosis who have undergone the pulse-dose cyclophosphamide treatment. The cases included 3 women, two with primary progressive multiple sclerosis (one, the classical form and the other, the spinal cord from). The 3rd case was that of myelitis-optic neuritic form and the total blindness of right eye (left side had been totally blind) was impending despite repeated corticosteroid therapies. The regimen included 600 mg/m2 intravenous cyclophosphamide per day at days 1, 2, 4, 6, 8 and infusion of totally 2,500-3,000 ml of intravenous fluid in order for avoiding hemorrhagic cystitis. The side effects were nausea, anorexia, leucopenia (10-15 days from the end of the course and the lowest value being 1,100/microliters), microscopic hematuria in one case, and alopecia in all. All the patients tolerated the therapy well. Two cases improved to a significant degree and the 3rd case with impending blindness has shown the arrest of progression. However, two of them began progressing again in one- to two-year period and the pulse-dose had to be repeated. These 3 cases have shown neurological improvements or at least arrest of the progression following the therapy.(ABSTRACT TRUNCATED AT 250 WORDS)