The effect of inhalation of cotton dust on the induction of nitric- oxide (NO) and the contribution of NO to oxidant generation were investigated. Sprague-Dawley-rats were exposed to air, a dust aerosol of cotton (40.6+/-3.7mg/m3), or aerosolized endotoxin (2.2x10(4) endotoxin units) for 3 hours. Responses were studied 18 hours after exposure in bronchoalveolar lavage fluid (BALF). BALF was analyzed for protein levels, lactate-dehydrogenase, and total nitrite levels. Both cotton dust and endotoxin produced an acute pulmonary inflammatory reaction, with increases in red blood cells, lymphocytes, and polymorphonuclear lymphocytes in BALF. The response was stronger for endotoxin than for cotton dust. Endotoxin and cotton dust elevated NO levels. A marked increase in nitric-oxide- synthase messenger RNA occurred following exposure to dust of cotton and endotoxin, and was confined to BALF. Endotoxin increased oxidant species as monitored by chemiluminescence, whereas cotton dust elevated zymosan stimulated and nitric-oxide-synthase dependent chemiluminescence. The authors conclude that endotoxin may be a major etiologic agent in the response to cotton or other organic dusts, but it is not the sole contributing factor in organic dust toxic syndrome.