The health hazards associated with grain dust exposure have been recognized as a cause of lung diseases. In the present study, we used germ-free rats exposed to AspergilIus versicoIor to elucidate the mechanism for the lung damage induced by grain dust exposure. One month after exposure to the mold, remarkable proliferation of bronchus-associated lymphoid tissues with germinal centres was induced by aspiration of mold spores. After 1 month, alveolar macrophages increased, becoming foamy macrophages by ingestion and digestion of mold spores. They expressed interleukin (IL)-I, Ia antigens and intercellular adhesion molecule-1 intensely and occasionally bound lymphocytes. Numerous lymphocytes infiltrated the granulomatous lesions which consisted of accumulated foamy macrophages and some T lymphocytes which carried IL-2 receptor. Granulomatous lesions were identified in the entire lung, especially around bronchioles. They extended from alveolar ducts to alveolar spaces for 6 months after exposure to the mold. The macrophage appears to be a key effector cell in granulomatous reactions to inhaled molds.