The effect of chronic sulfur dioxide (SO 2) inhalation was investigated in pharmacologic-induced bronchoconstruction in beagle dogs. Increase in pulmonary resistance (R L) and decrease in dynamic lung compliance (C DYN) were observed with i.v. and aerosol administration of prostaglandin F 2α (PGF 2α). After control historical data were accumulated, the animals received exposures of 500 ppm of SO 2 for two hours twice a week. After six months of chronic SO 2 exposure, a significant enhancement in the R L response to i.v. and aerosolized PGF 2α was observed as compared to pre-SO 2 data. Tracheobronchial inflammation, as observed by fiberoptic bronchoscopy, occurred as a result of the chronic inhalation of SO 2; however, only a small increase in mucous production was observed visually. In additon, hypercapnic and acidotic changes in blood gas profiles were found. Therefore, beagle dogs chronically exposed to SO 2, developed hyperactive airways as seen by increased sensitivity to PGF 2α. This model appears to reflect many of those changes observed in clinical bronchial hyperreactivity and may provide an additional insight into obstructive disease.