Experimental allergic encephalomyelitis (EAE) is an autoimmune disease characterized by inflammation and demyelination in the central nervous system (CNS). Administration of transforming growth factor-beta (TGF-beta) has been shown to inhibit EAE. In this study, the possible role of endogenous TGF-beta in the regulation of relapsing EAE produced by the transfer of myelin basic protein-specific T cell lines was assessed. Although TGF-beta is not present in the normal CNS, this cytokine was detected by immunohistology in areas of central nervous system inflammation in both acute and chronic disease. The administration of anti-TGF-beta at the disease onset led to a worsening of the clinical course of EAE and more extensive pathological lesions. These findings provide direct evidence for a role of endogenous TGF-beta in the remissions seen in chronic relapsing EAE.