Experimental allergic encephalomyelitis (EAE) is considered the animal disease model for multiple sclerosis (MS) in humans. However, EAE is an acute disease whereas MS is a chronic disease. The on-off nature in both diseases of autoimmune reactivity suggests a regulatory response by the host, a response which can effect the autoreactive T cell by modulating-up or modulating-down. This review discusses various aspects of this regulation, seen after administration of autoantigen, of antibody directed at the T cell receptor (TcR), and of fragments of the TcR itself.