Reliable laboratory prognostic factors for MS are still lacking. The predictive value of markers of T-cell activation for long-term disease progression was investigated. Flow cytometry measurements were correlated to changes in Expanded Disability Status Scale and MR T2 lesion load over 36 months in 14 patients with secondary progressive MS. A correlation was found between the percentage of tumor necrosis factor-alpha-producing CD4(+) T cells at baseline and the change in T2 lesion load during 3-year follow-up (r = 0.79, adjusted r(2) = 0.59, p = 0.001).