Defense mechanisms protect the lung very well from inhaled organic dusts. With sufficient exposure to certain dusts, however, susceptible individuals develop hypersensitivity pneumonitis (HP), the organic dust toxic syndrome (ODTS), or asthma. Mucous membrane irritation (MMI) bothers some individuals inhaling grain dust. Allergic asthma is caused by IgE-mediated immunologic responses to allergenic dust contaminants. ODTS can be explained by a nonimmunologic release of interleukin 1 (IL-1) and perhaps other endogenous pyrogens from alveolar macrophages by endotoxin or other ingredients of dusts. The pathogenesis of HP may involve IL-1 release combined with a specific immunological response by effector T-lymphocytes. MMI may be the result of an irritant effect not involving immune responses or mediators.