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Objectives: Migration of inflammatory cells across the blood-brain barrier is a central event in the formation of multiple sclerosis (MS) lesions and is known to be enhanced in MS patients. This study investigates the migration of CD4+ and CD8+ T-cell subsets and the effects of interferon-beta1a (IFN-beta1a) treatment on migration and matrix metalloproteinase-9 (MMP-9) production of these T-cell subsets., Materials and Methods: An ex vivo transwell system was established to compare the migratory behaviour of lymphocytes isolated from normal controls and untreated MS patients. In addition, MS patients were investigated longitudinally after initiation of IFN-beta1a treatment., Results: Migration of CD4+ T cells (P < 0.05), but not of CD8+ T cells, was enhanced in untreated MS patients compared with controls and was normalized by treatment with IFN-beta1a. In addition, IFN-beta1a treatment reduced MMP-9 production of CD4+ but not CD8+ T cells., Conclusion: Our results indicate that CD4+ T cells, but not CD8+ T cells, contribute to the enhanced ex vivo migration observed in MS.