Guinea pigs were exposed chronically for 6 hr/day, 5 days/week for 52 weeks to cotton dust at 21 mg/m³. The animals developed a severe pulmonary response following the first day of exposure. With continued exposure, three phases of response were noted which may be compared with grades of byssinosis noted in cotton workers. An early stage, up to 3 months of exposure, was characterized by response on Mondays, analogous to Grades ½-1 byssinosis. An intermediate stage, from 4-6 months, was characterized by pulmonary response on Monday and responses on other weekdays. Airflow obstruction was also present at this stage. This stage may be compared with Grade 2 byssinosis. A chronic stage from 6 months on was characterized by daily responses, severe airflow obstruction and reduced baseline pulmonary function. This stage is analogous to Grade 3 byssinosis. The animal model was therefore able to display each of the stages of respiratory response reported for byssinotic workers and to demonstrate the progression of disease from one phase to the next.