We evaluated whether new multiple sclerosis (MS) lesions with variable durations of enhancement have different magnetization transfer ratios (MTR) at the time of their appearance. We scanned ten patients with relapsing-remitting MS every four weeks on four occasions. During each of the monthly sessions, we obtained dual echo, MT and T1-weighted scans. Five minutes after gadolinium-DTPA (Gd) injection, another T1-weighted scan was obtained. We measured the MTR of new enhancing lesions on co-registered quantitative MTR images. During the three-month follow up, 54 new enhancing lesions were seen with a mean MTR value of 33.6% (SD=7.8%). The mean MTR values were 35.3% (SD=7.0%) for lesions enhancing on only one scan and 29.3% (SD=8.6%) for those enhancing on at least two consecutive scans (P=0.01). These results suggest that enhancing lesions in MS have heterogeneous pathological substrates, which may be associated with different durations of the enhancing phase.