OBJECTIVE Young C57BL/6 (B6) mice were treated with a specific tolerogen-dual analogue (Lys262-Ala207) intranasally to observe its effect on the invasion process of mice model and the clinical symptoms, to assess its clinical effects, and to explore the underlying mechanisms and feasibility of nasal mucosal tolerance explored. METHODS Passively transferred myasthenia gravis (PTMG) was induced by mAb35 on B6 young female mice. Sixty mice were divided equally into three groups: tolerance group, model group and control group. Lys262-Ala207 was given intranasally (250 microg/mouse) to tolerance group with mAb35 for 10 successive days before immunization. Model group received PBS 50 microl only. The body weight and clinical scores were evaluated. The serum levels of AChRAb and the main cytokines (IL-4, IFN-gamma, TGF-beta1) were detected with ELISA. RESULTS The model group had typical myasthenia symptoms. B6 mice of tolerance group had less severe symptoms compared with control groups. The clinical symptoms of tolerance group were relieved. The level of AChRAb in tolerance group [(16.01 +/- 1.09) mg/L] was significantly lower than that of model group [(28.12 +/- 1.28) mg/L] (t = 44.37, P < 0.01). IL-4 and IFN-gamma levels in tolerance group [(141.02 +/- 3.11) ng/L, (187.99 +/- 4.67) ng/L] were significantly lower than those of model group [(193.37 +/- 3.95) ng/L, (320.46 +/- 2.14) ng/L] (t = 37.20, 51.69, P < 0.01). The level of TGF-beta1 in tolerance group [(437.19 +/- 1.93) ng/L] was higher than that of model group [(175.63 +/- 3.12) ng/L] (t = 36.07, P < 0.01). But there were still significant change as compared to those in control group (t = 26.65, 31.05, 49.02, P < 0.01). CONCLUSIONS Nasal administration of Lys262-Ala207 ameliorated muscular weakness in PTMG young mice. The therapeutic effect is possibly correlated with the function of immune system.