Inhalation of cotton dust has been associated with development of byssinosis. An animal model has been described recently in which guinea pigs exposed to cotton dust for a 6-week period demonstrated acute respiratory reactions consisting of increased breathing frequency, reduced tidal volume, and airflow fluctuations most prominent on the first day of exposure following a period without exposure, often referred to as a "Monday" response (Ellakkani et al., 1984). The current study examined the effects of cotton dust inhalation for 52 weeks in order to evaluate the animal model for ability to demonstrate more chronic effects of cotton dust exposure. Twenty guinea pigs were exposed to 21 mg/m3 cotton dust for 6 hr/day, 5 days/week, for 52 weeks. Twenty control animals received sham exposure. Parameters used to indicate chronic effects included respiratory measurements, weight gain, lung volume and weight, and histopathological evaluation. Respiratory measurements were taken while animals were breathing ambient air and also while breathing a mixture of 10% CO2, 20% O2, and 70% N2. Pulmonary effects were noted to change during the 12 months of exposure. For the first 3 months experimental animals displayed an increase in breathing frequency and a decrease in breathing volume measured as whole-body plethysmographic pressure. These effects were pronounced on the "Monday" of each week. During Months 3-6, reactions occurred on each day of exposure, although Monday responses were most severe. After 6 months, respiratory reactions were pronounced daily. Other indications of a chronic effect of exposure were increased lung volume, measured by water displacement, 15.0 +/- 3.3 ml (mean +/- SD) for the exposed group, compared with 9.8 +/- 2.0 ml for the controls; increased lung weight 9.4 +/- 1.5 g vs 7.0 +/- 0.8 g; and bronchiolar epithelial hyperplasia and hyperplasia of alveolar type II cells. Additionally, a histomorphometric study of the lungs performed by others (Coulombe et al., 1986) detected changes in the peripheral conducting airways, including increased thickness of bronchiolar epithelium and increased thickness of septa at the alveolar level, denoting chronic exposure. Taken together, these results indicated chronic respiratory effects in guinea pigs as a result of 52 weeks of continued exposure to cotton dust. The parallel in development of symptoms in guinea pigs and in humans exposed to cotton dust indicates that the guinea pig is a suitable model for byssinosis.