We exposed 10 guinea pigs to respirable Cotton dust for 6 hours/day, 4-5 days/week, for 8-10 weeks. Specific airway conductance (S(Gaw)) measured prior to each day's exposure did not change. There was a fall in S(Gaw) after each day's exposure which averaged 19.3 ± 8.7 percent (mean ± S.D., p=0.022). Responsiveness to inhaled methacholine decreased with chronic exposure. Baseline ED(50)--the concentration of nebulized methacholine which produces a 50 percent decrease in SGaw--increased from 1.57 + 0.25 to 5.04 1.63 mg/ml (geometric mean + S.D., p=0.020). With each daily exposure, there was a transient increase in ED(50) of 43.3 + 24.0 percent (p=0.051). There were no significant changes in the SGaw or ED50 with sham or cellulose dust exposure except for a small increase in baseline ED50 in the cellulose dust exposure group. Respiratory rate changed little with exposure except on the first day of each week when it increased from 111 to 122/min (p=0.066). There was no work-week effect noted for changes in S(Gaw) or ED(50)-Bronchoalveolar lavage performed at the end of exposure showed a large increase in total cell count and neutrophil percent (35.4 + 15.5 x 106 36 9 + 10.4 percent, respectively; vs. 4.6 + 2.0 x 109, 1:3 T 0.7 percent in sham exposed controls; P<0.0001 and p=0.0001, respectively). Histologic examination showed peribronchiolar lymphocytic infiltration, intra-alveolar accumulation of neutrophils and macrophages and alveolar wall thickening. We conclude that alterations in airway function can be observed in this animal model of cotton dust exposure. Further, these changes may be mediated by inflammation in the airways and lung parenchyma.