Bronchial hyperreactivity (BHR) is associated with the presence of airway inflammation in asthma and is seen in individuals occupationally exposed to grain dust. To better understand the relationship between BHR and pulmonary inflammation after grain dust exposure, we carried out an inhalation challenge to corn dust extract (CDE) on seven subjects with BHR [a 20% or greater decrease in forced expiratory volume in 1 s (FEV(1)) compared with diluent FEV(1) with a cumulative dose of histamine </=47.3 breath units] and compared their physiological and inflammatory responses with those of seven matched control subjects. BHR subjects were exposed to nebulized CDE (target dose of 0.16 microg/kg endotoxin) as tolerated; matched controls received equal amounts of CDE. Subjects with BHR complained of chest tightness and dyspnea within the 2 h after inhalation of CDE significantly more frequently than controls. Similarly, subjects with BHR developed significantly greater percent declines in FEV(1) at time points up to 4 h after exposure to CDE. Significant increases in total cells, neutrophils, tumor necrosis factor-alpha, interleukin-6, and interleukin-8 were detected in bronchoalveolar lavage fluid 4 h after inhalation of CDE in all subjects, but no differences were detected between the control and BHR groups. These results suggest that, although subjects with BHR develop a more precipitous decline in FEV(1) after exposure to CDE, the inflammatory response to CDE is similar in subjects with and without BHR.