The guinea pig model has been found useful to evaluate cotton dusts for potency in producing acute respiratory effects. In this study, the model was used to assess the effects of several physical and chemical treatments to reduce the acute respiratory responses due to inhalation of cotton dust. Dust was treated with ethanolic solutions, gamma irradiation or ozone. Treatment of dust in either acidic or alkaline ethanolic solutions reduced its endotoxin activity as measured by the Limulus amebocyte lysate gelation assay. However, only the alkaline treatment significantly reduced the pulmonary toxicity of the dust. Ozone treatment, and gamma irradiation of dust reduced neither the endotoxin activity nor pulmonary toxicity of the cotton dust. These results indicate that the animal model is applicable to assess treatments for reducing pulmonary reactions to cotton dust.