Silicosis provides a good model for chronic interstitial pulmonary inflammation. In order to clarify the role of mast cells in the development of interstitial lung diseases, silica suspension was transnasally administered to mast cell-deficient mice (WBB6F1-W/Wv) and their mast cell-intact littermates (WBB6F1(-)+/+) as well as to normal mice (C57BL/6). Histologic examinations and analyses of bronchoalveolar lavage fluid (BALF) components indicated that silica instillation induces less severe lung lesions in mast cell-deficient mice than in mast cell-intact mice. BALF neutrophilia was prominent in mast cell-intact mice, but mast cell-deficient mice developed significantly milder BALF neutrophilia. An increase in the number of lung mast cells was observed in mast cell-intact mice. To further prove the involvement of mast cells, bone marrow-derived cultured mast cells from +/+ mice were adoptively transferred to mast cell-deficient mice. These mast cell-reconstituted mice developed more severe pulmonary lesions than did the mast cell-deficient mice; the severity of the lesions was similar to that in mast cell-intact mice. In addition, BALF neutrophilia was elicited by mast cell reconstitution. A significant number of mast cells was found in the lungs of mast cell-reconstituted mice when silica was administered. These results suggest the involvement of mast cells in the development of silicosis and implicate interactions between mast cells and neutrophils in the pathogenesis of this disorder.