We examined the effect of Copolymer-1 (Cop1) on magnetic resonance (MR) imaging changes in 10 patients with relapsing-remitting multiple sclerosis (RRMS). Monthly gadolinium (Gd)-enhanced MR imaging was performed for 9 to 27 months in the pretreatment period followed by 10 to 14 additional months during Cop1 treatment. MR images were evaluated by two radiologists (F.S. and R.C.P.) masked to the scan date. We found a 57% decrease in the frequency of new Gd-enhancing lesions and in the mean area/month of new Gd-enhancing lesions in the Cop1 treatment period compared with the pretreatment period (0.92 versus 2.20 lesions per month and 22 mm2 versus 43 mm2 area/month; p = 0.1, Wilcoxon signed rank test). Percentage change in lesion load area on T2-weighted images showed a decrease in the accumulation of lesion area during treatment, which was significant for the patient group with a longer pretreatment period (p = 0.05, Friedman test). These results demonstrate a reduction in the number of new Gd-enhancing lesions and in the lesion load during Cop1 treatment compared with the preceding period without therapy and are suggestive of an effect of Cop1 on MR abnormalities observed in multiple sclerosis.