A murine animal model was utilized to demonstrate the involvement of endotoxin in the development of acute pulmonary inflammation following inhalation of cotton dust. Endotoxin sensitive C3HeB/FeJ and endotoxin resistant C3H/HeJ mice were exposed for 6 hr to atmospheres of either 45 mg/m³ cotton dust or 208 µg/m3 (nominal concentration) lipopolysaccharide (LPS) from Enterobacter agglomerans. Inflammation was assessed by bronchoalveolar lavage (BAL) cellularity and lung histology. A neutrophil influx into the airways was produced by each agent in C3HeB/FeJ mice, whereas no inflammation resulted in C3H/HaJ mice from inhalation of LPS, and minimal inflammation followed exposure to cotton dust. These results suggest a major role of endotoxin in acute inflammation induced by cotton dust inhalation.