To elucidate the possible involvement of nitric oxide (NO) derived from inducible NO-synthase (iNOS) in the pathogenesis of patients with allergic rhinitis, we analyzed changes in the frequency of sneezing, plasma levels of NO metabolites, α-melanocyte-stimulating hormone (MSH) and immunoglobulin E and tracheal expression of IgA and mast cell tryptase in control and iNOS^−/− mice. Eight-week-old control and iNOS^−/− male C57BL/6j mice were sensitized with Cry j I antigen. After the last intranasal challenge of antigen, changes in the frequency of sneezing and plasma levels of IgE, α-MSH and NO metabolites and tracheal expression of iNOS, IgA and mast cell tryptase were analyzed by ELISA and immunohistochemistry using specific antibodies. The sensitization of mice with Cry j I antigen increased plasma levels of NO metabolites, α-MSH and IgE and tracheal expression of iNOS, IgA and mast cell tryptase in control not but in iNOS^−/− mice. Administration of N ^G-nitro-L-arginine methyl ester strongly inhibited all these changes occurred in control mice. These results indicate that the symptom of pollinosis including sneezing is enhanced by iNOS derived NO through activation of α-MSH-receptor containing mast cells enriched with tryptase.