Guinea pigs exposed to high levels of cotton dust (35 mg/m³ for 2 hrs) exhibited changes in the following pulmonary parameters: 1) increased CO₂ challenged breathing rate, 2) increased number of ravaged leukocytes, 3) decreased number of lavaged alveolar macrophages, and 4) enhanced activity of alveolar macrophages. In the present study, we constructed relationships for these pulmonary responses vs the airborne concentration of cotton dust. Guinea pigs were exposed to various levels of cotton dust (0.4 - 32.4 mg/m³) for 6 hrs. Pulmonary measurements were made 18 hrs post-exposure. CO₂ challenged breathing rate exhibited a strong relationship to exposure dose. However, exposure-induced increases in breathing rate were not significant at dust levels below 2.2 mg/m³. In contrast, cotton dust-induced increases in pulmonary leukocyte number and alveolar macrophage activity were discernable at dust levels as low as 0.4 mg/m³. Therefore, measurement of the cellular response of guinea pigs to cotton dust inhalation seems to be a more sensitive indicator of the acute pulmonary response than changes in CO₂- challenged breathing rate.