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Lymphokine activity in seven myelin basic protein (MBP)-specific T cell clones was examined. All of the clones recognize MBP peptide 1–9 in the context of I-A^u. A strong positive correlation was found between levels of lymphotoxin (LT) and tumor necrosis factor alpha (TNF-α) mRNA and biological activity on L929 cells and their capacity to Induce paralysis, the clinical hallmark of experimental allergic encephalomyelitls (EAE). No correlation was found between interleukin-2 or gamma interferon production and encephalitogenicity. LT and/or TNF-α may play a central role in the pathogenesis of EAE.