To determine whether atopy influences the physiologic or inflammatory response to grain dust, we compared spirometric measures of airflow and bronchoalveolar lavage (BAL) measures of lower respiratory tract inflammation between demographically similar nonatopic (n = 10) and atopic (n = 10) study subjects after each of two inhalation exposures: Hanks' balanced salt solution (HBSS) and corn dust extract (CDE; 0.4 microgram of endotoxin/kg body weight). Subjects were healthy nonsmokers with similar baseline pulmonary function, without bronchial hyperreactivity, and had not participated in agriculture. Atopic subjects had two or more positive skin responses to 10 common environmental allergens. Both groups developed significant airflow obstruction and lower airway inflammation after CDE inhalation. Importantly, the magnitude of the post-CDE exposure airflow decrements, BAL cellularity, and BAL concentration of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), IL-6, and IL-8 did not significantly differ between atopics and nonatopics. The concentrations of histamine and eosinophils in the BAL fluid were unaffected by CDE inhalation and did not significantly differ between atopics and nonatopics. Atopic status does not appear to be a significant determinant of airflow obstruction or lower airway inflammation following CDE inhalation. Our findings suggest that atopy may play, at most, a minor role in the development of grain dust-induced airway disease.