Experimental autoimmune encephalomyelitis is a long-established mouse model of multiple sclerosis. The requirements for autoreactive T-cell activation in this disease have been characterized extensively and novel strategies for immune-intervention are being developed continually. Notably, identification of immunodominant T-cell epitopes allows the induction of T-cell tolerance with synthetic peptides. Several transgenic mouse lines that express transgenic T-cell receptors recognizing myelin autoantigenic epitopes have been developed. These allow adoptive transfer studies to analyse the activation of naïve autoreactive T cells in vivo during the induction of tolerance vs immunity. More recently, our attention has focused on immune mechanisms underlying the natural recovery from disease. Sampling of the lymphoid cell infiltrate within the central nervous system has identified the accumulation of regulatory T cells in the target organ during this period of resolution.