Acute disseminated encephalomyelitis (ADEM), a postinfectious illness of the central nervous system (CNS), is thought to be an autoimmune disease. Here, we characterized the cytokines secreted by myelin-reactive T cells generated from patients with ADEM. The frequency of MBP-reactive T cell lines was ten-fold higher in patients with ADEM compared to patients with encephalitis and normal subjects. Whereas there was no significant IFN-gamma secretion, the predominant cytokine secreted by MBP-reactive T cell lines was IL-4 in patients with ADEM. In contrast, IL-4 secretion was only rarely detected in the controls. The presence of high frequencies of MBP-reactive IL-4 secreting T cells in subjects with ADEM during their recovery phase may be similar to myelin reactive IL-4 secreting T cells observed during the spontaneous recovery of animals with EAE.