The objective of the present experiments was to study the effects of pulmonary inflammation induced by subacute Sulfur-dioxide (SO 2 ) exposure on capsaicin-induced responses in isolated primary vagal sensory neurons and cough. Additionally, we examined the effects of SO 2 exposure on respiratory function and lung histology. All experiments were conducted 24h after 4 days of subacute SO 2 (1000ppm, 3h/day for 4 days) exposure. In in vitro experiments, intracellular Ca 2+ concentrations were measured in single nodose ganglia cells isolated from SO 2 treated and control guinea pigs, using a fluorescence-based methodology. In nodose ganglia cells from SO 2 -exposed animals, intracellular Ca 2+ responses evoked by capsaicin (1×10 −7 and 1×10 −6 M) were significantly augmented (87% and 59%, respectively) compared to nodose ganglia from control animals. In vivo experiments, cough responses induced by a submaximal dose of aerosolized capsaicin (30μM) were increased approximately 50% in SO 2 exposed animals compared to control animals. The enhanced cough response produced by SO 2 was inhibited by the corticosteroid, dexamethasone (10mg/kg, p.o. b.i.d for 4 days and 10mg/kg, p.o. once on day 5). In separate experiments, guinea pigs exposed to SO 2 displayed a decrease in respiratory frequency and minute ventilation and an increase in enhanced pause (PenH), a surrogate measure for pulmonary obstruction. Associated with the SO 2 -induced increase in cough and changes in respiratory parameters was an increase in BAL neutrophils. BAL neutrophil counts were 5±4 and 691±141 cells×10 3 /ml for air and SO 2 -exposed animals, respectively. The neutrophillic inflammation induced by SO 2 was attenuated by dexamethasone treatment. Finally, staining for collagen, smooth muscle and goblet cells showed inflammation, remodeling and goblet cell metaphasia in the SO 2 -exposed animals. Our results demonstrate that SO 2 exposure enhances TRPV1 receptor function at the level of the nodose ganglia. This effect occurs in parallel with an increase sensitivity of the cough response to capsaicin.