We have previously shown that naive healthy subjects challenged with cotton bract extract (CBE) exhibit physiologic changes of airway hyperresponsiveness as well as characteristic "Monday Bronchospasm." CBE represents a major component of cotton dust and is thus potentially an important model for the study of byssinosis. In 11 healthy, non-smoking subjects (8 male, 3 female, age = 31.6 + 2.7) we examined in a double-blind random order, the effects CBE and cotton dust extract (CDE) for two hours following a ten minute aerosol inhalation. Endotoxin levels were 5.71 EU/mg for CBE and 31.88 EU/mg for CDE; oxFMLP levels were 90.2 g/mg for CBE and 31.88 EU/mg for CDE. Challenges were separated by one week. The response to methacholine (MC) two hours following CBE or CDE was also measured. Lung function was recorded using maximal and partial flow volume curves. On the latter we measured the maximal expiratory flow 60% of baseline vital capacity below total lung capacity (MEF40%(P)). Responders (R) were defined as subjects who developed a 20% or greater fall in MEF40%(P) following extract challenge. There were 8 responders to CBE and 9 responders to CDE. All CBE responders were CDE responders. The average maximal response to CBE was a fall of MEF40%(P) to 68 + 9.1% of baseline compared to 68 + 6.8% for CDE (NS). All subjects R and non-responders (NR) enhanced their MC response following CBE or CDE. The PD40 MEF20%(P) was the same for CBE and CDE, 1.3 mg/cc. We conclude that CBE and CDE exert similar physiologic effects in naive healthy subjects.