Objective: To determine whether lesion evolution in relapsing-remitting multiple sclerosis (RRMS) patients is altered by treatment with interferonβ-1b (IFNb-1b) or by intravenous methylprednisolone (IVMP) as measured by magnetization transfer imaging. Methods: Magnetization transfer ratios (MTR) of 225 contrast enhancing lesions (CEL), in four RRMS patients were serially determined for 12 months before and 12-18 months after contrast enhancement in a baseline vs treatment trial with IFNβ-1b. During the baseline period, 185 new CEL were identified: 76 were treated with IVMP (1 giday x 5 days) and designated steroid CEL (S-CEL); the remaining 109 were considered baseline lesions (B-CEL). During IFNβ-1b treatment, 40 CEL (IFN-CEL) were identified. After image co-registration, regions of interest (ROIs) defining new CEL were transferred to the MTR image set to determine the mean lesion MTR on each monthly exam. The lesion MTR was compared to MTR of normal appearing white matter (NAWM) on the same exam. Results: As early as 12 months prior to enhancement, the MTR of CEL was reduced compared to NAWM (mean 9.43±3.2%; P<0.001). The further reduction in MTR (28%±4.0) at the time of contrast enhancement was not significantly different for B-CEL, S-CEL or IFN-CEL. Following enhancement, lesion recovery for IFN-CEL (P=0.02) and S-CEL (P=0.002) was significantly higher than B-CEL. Conclusion: IFNβ-1b and IVMP reduce tissue damage and promote lesion recovery in RRMS patients. The additional benefit of IVMP compared to IFNβ-1b may be related to its inhibitory effect on demyelination.