Biomarkers that allow the identification of patients with multiple sclerosis (MS) with an insufficient response to immunomodulatory treatment would be desirable, as currently available treatments are only incompletely efficacious. Previous studies have shown that the expression of CD25, CD26 and CCR5 on T cells is altered in patients with active MS. We studied the expression of these molecules by flow cytometry in patients followed for six months during immunomodulatory treatment. In interferon (IFN)-beta-treated patients, we found that the hazard ratio for developing an attack was 28 in patients with CD26 + CD4 + T cell counts above median, and this risk was independent of the risk conferred by neutralizing anti-IFN-beta antibodies. CD26 + CD4 + T cell counts may identify patients with MS at increased risk of attack during treatment with IFN-beta.