The objective of this investigation was to compare the pulmonary response of the guinea pig to inhalation of agricultural dusts and cotton dust. The four agricultural dusts chosen for study were generated from samples of silage or hay which had resulted in cases of organic dust toxic syndrome in farm workers. A typical response of the animal model to inhalation of cotton dust (11.6mg/m³ for 6 hrs) included: elevated breathing rate, infiltration of neutrophils and lymphocytes into the airspaces, enhancement of zymosan-stimulated superoxide release from alveolar macrophages, and airway closure. Inhalation of silage or hay dusts (5.9-11.6mg/m³ for 6 hrs) resulted in analogous reaction profiles. The results indicate that the guinea pig animal model should be useful in evaluating pulmonary reactions to agricultural dusts. Furthermore, these data suggest a possible commonality among organic dusts as to etiologic agent(s) and mechanisms of pulmonary response.