Experimental autoimmune encephalomyelitis (EAE) is a T cell-mediated autoimmune disease commonly employed as a model for multiple sclerosis. Extensive studies have demonstrated that EAE may be prevented or ameliorated by the intranasal administration of soluble peptides representing encephalitogenic epitopes. There is increasing evidence that this peptide administration may function via the generation of regulatory cells. The mechanism of action of these cells remains controversial and it seems likely that it may vary between experimental models. At present the majority of work on regulatory cells has centred on characterising naturally occurring regulators, or those generated artificially ex vivo, and less is known about induced regulatory cells produced following peptide administration. This report aims to briefly outline the evidence for the existence of natural regulatory T cells and to introduce the sub-types of induced regulatory T cells now recognised. In several of these regulatory cell systems investigated to date, interleukin-10 (IL-10) has been shown to be important in cell function. This has not been directly investigated in a model employing peptide therapy to induce peripheral tolerance, hence the purpose of this study was to investigate the role of IL-10 in the generation of these regulatory cells. This work has employed both a TCR transgenic mouse system, for predominantly in vitro studies of cell function, and an IL-10 knock-out mouse strain to investigate in vivo disease protection. The results summarised in this report demonstrate that IL-10 is fundamentally important in the generation of disease protection following intranasal peptide therapy.