Matrix metalloproteinases and their tissue inhibitors play a key role in the pathogenesis of adult-onset multiple sclerosis, and were suggested as biomarkers of response to interferon-beta, an established treatment in multiple sclerosis. However, data regarding pediatric population are scarce. We determined serum levels of matrix metalloproteinase-7, matrix metalloproteinase-9, and tissue inhibitor of matrix metalloproteinase-1 in children, and evaluated effects of interferon-beta therapy on these measures. Serum samples from 14 children with relapsing, remitting multiple sclerosis at baseline and at month 12, and from 15 controls, were collected. Interferon-beta treatment was initiated in eight patients. Mean serum matrix metalloproteinase-9 levels and matrix metalloproteinase-9/tissue inhibitor of matrix metalloproteinase-1 ratio were higher in patients compared with controls, and were reduced significantly in treated patients at month 12, but did not change in untreated patients. Mean matrix metalloproteinase-7 levels were lower in patients compared with controls, and increased significantly in the treated group, but did not change significantly in the untreated group. In pediatric multiple sclerosis, a shift in matrix metalloproteinase9/tissue inhibitor of matrix metalloproteinase-1 balance toward proteolytic activity is evident, and interferon-beta therapy demonstrates a beneficial effect on this disturbed balance. (C) 2012 Elsevier Inc. All rights reserved.