Dampness and mold growth in buildings cause spore generation into indoor air, which is associated with respiratory tract disorders. Specific agents or cellular mechanisms of diseases have not yet been identified. In this study, airborne spores of Streptomyces sp., isolated from moldy houses, stimulated RAW264.7 macrophages, which produced tumor necrosis factor alpha and interleukin-6 and induced the expression of inducible nitric oxide synthase, with subsequent nitric oxide production. Spores of other microorganisms typically found in moldy houses did not markedly increase the production of these inflammatory mediators. The data implied a mechanism by which Streptomyces sp. may lead to respiratory tract disorders in individuals who live in moldy houses.