MS is a T-cell-mediated demyelinating disease of the CNS, in which the cytokine network may be deranged, leading to an altered immunoregulation. Tumor necrosis factor alpha (TNF-alpha) is a cytokine with several effects on the neuroimmune system. There are specific TNF-alpha receptors on human lymphocytes and other cell types, even in the CNS. We assayed TNF-alpha binding on peripheral blood T cells from MS patients compared with healthy subjects. T cells from MS patients have significantly more TNF-alpha receptors than those from control subjects (Bmax, 955 +/- 31 versus 126 +/- 3 [mean +/- SEM] receptors per cell). Such TNF-alpha binding sites are of the same type in patients and healthy subjects (Kd, 68.7 +/- 4.8 versus 70.2 +/- 4.1 [mean +/- SEM]pM). We discuss these results in terms of MS immunopathogenesis, because activated T cells have increased amounts of TNF-alpha receptors.