Serial gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) was used to monitor the effect of mitoxantrone in ten patients with rapidly deteriorating multiple sclerosis (MS). MRI was performed as a baseline and thereafter at 1, 3, 6, 9, 12 and 24 months. The total number of Gd-enhancing lesions diminished from 169 at baseline to 10 after 1 year and to 5 after 2 years. This reduction and the percentage of follow-up MRI studies showing no Gd enhancement were more pronounced than in other MRI studies of the natural course of MS. Measured with quantitative neurological scales, only one patient showed deterioration after 2 years; nevertheless, the changes in MRI were much more marked than those observed clinically. Serial Gd-MRI therefore, seems necessary for documenting efficacy in future therapeutic trials.