Tolerance to B cell-mediated experimental autoim-mune myasthenia gravis (EAMG), an animal model for myasthenia gravis (MG) in human s, can be achieved byn asal adminis tra tion of the autoantigen acetylcholin ereceptor (AChR). Nasal tolerance induction requiresonly l/1000 0f the amount of AChR used for oral toler-ance in ductio n, but is as effe ctive in preventing EAMG.To investigate whether nasally induced tolerance toEAMG can be inOuenced by nasal administration ofcytokin es, recom bin ant rat IFN -y (total 5000 U/ra t), acombination of AChR and IFN-'y or AChR alone was given nasally to Lewis rats before immunization withAChR and complete Freun d's adjuvant (CFA). One ad-ditional group of rats received the same amount ofAChR nasally in conjunction with IFN-y (total5000 Ulrat) intraperitoneally. AChR given alone nasally in-duced effective tolerance to EAMG whereas rats re-ceiving AChR + IFN-y by the nasal route exhibited asimilar disease pattern, and similarly escalated T andB cell responses to AChR when compared to controlEAMG rats. In contrast, administration of IFN-y ip to-gether with AChR nasally did not affect the inductionof tolerance to EAMG. IFN-'y given alone nasally didnot affect clinic al EAMG. This study demonstrates th at nasal tolerance can be modulated by nasal administra-tion of minute amounts of IFN- y. Nas al adminis trationof certain cytokines with benemial effects mightbroaden the effectiveness of applying nasal toleranceas a poten tial therapeu tic means of preventing au toim-mune diseases..