Mitoxantrone is an anthracenedione anti-neoplastic agent that has recently been shown to be effective in ameliorating disease activity in multiple sclerosis (MS) as indicated by clinical and MRI data. However, the role of mitoxantrone in escalating treatment of patients with frequent and severe relapses and with rapid progression of disability is less clear. In this retrospective analysis we report on 15 patients with severe relapsing-remitting (9 patients) and secondary progressive MS with superimposed exacerbations (6 patients) treated open-labeled with mitoxantrone in our Clinical Research Group from July 1994 to October 1998. Eleven of these patients (73%) were treated with azathioprine, interferon-beta-1b or cyclophosphamide before. The patients received mitoxantrone over a period of at least 12 months (19 +/- 6 months) with a single dose of 10 mg/m2 monthly for the first three months. Thereafter, infusions were repeated every 3 months (total dose 141 mg +/- 45 mg). The annual relapse rate could be significantly reduced from 3.0 +/- 1.5 in the year before therapy to 0.5 +/- 0.5 during therapy. Nine patients (60%) were stabilised, while four patients (27%) showed an improvement of disability. The treatment was well tolerated with only minor side effects. These results although retrospectively obtained confirm previous trials showing that mitoxantrone may be useful in MS patients with frequent and severe exacerbations and/or a rapidly progressive course of the disease who have had other immunomodulatory medication.