Experimental autoimmune myasthenia gravis(EAMG) is caused by autoantibodies against the nicotinicacetylcholine receptor (AChR) at the neuromuscularpostsynaptic membrane and represents an animalmodel of myasthenia gravis in human. Recentstudies highlighted the roles of TH1 cytokines (IFN-g,IL-12), rather than TH2 cytokines (IL-4), in the pathogenesisof EAMG by using homozygous (2/2) knockoutmice with an EAMG-susceptible genetic background.To further evaluate a role for IFN-g, we injected recombinantrat IFN-g (rrIFN-g) at the time of immunizationwith AChR in complete Freund’s adjuvant toEAMG-susceptible Lewis rats and EAMG-resistantWistar Furth (WF) rats. RrIFN-g enhanced Lewis ratEAMG. The exacerbated muscular weakness was associatedwith higher levels of anti-AChR IgG and enhancedTNF-a responses. Anti-AChR IgG antibody levelswere augmented to a similar extent as in Lewirats, however, the identical immunization and IFN-ginjection induced only mild and transient EAMG inWF rats due to the default TH3 phenotype developmentand inherent low TH1 responses. We conclude that IFN-g plays a major role in the pathogenesis ofEAMG in the Lewis rat, but fails to break disease resistancein the WF rat.