Bronchopulmonary C-fiber afferents are characterized by their distinct sensitivity to chemical stimuli in the airways or pulmonary circulation. Responses evoked by activating these afferents are mediated by both central reflex pathways and by local or axon reflexes involving the release of tachykinins from sensory endings. Bronchopulmonary C-fiber stimulation reflexly reduces tidal volume and increases respiratory rate, constricts the airways, increases mucus secretion in the airways, and is associated with coughing. Cardiovascular effects include bradycardia, a fall in cardiac output, and bronchial vasodilation that increases airway blood flow despite systemic hypotension. In animals, C-fiber stimulation inhibits skeletal muscle activity, and in humans, is accompanied by burning and choking sensations in the throat and upper chest. Recent studies have identified additional physiologic and pharmacologic stimuli to these afferents, such as hydrogen ions, adenosine, reactive oxygen species, and hyperosmotic solutions. Furthermore, increasing evidence indicates that the excitability of these afferents is enhanced by the local release of certain autocoids (e.g. PGE2) during airway inflammation. These findings further indicate that vagal C-fiber endings in the lungs and airways play an important role in regulating the cardiopulmonary functions under both normal and abnormal physiologic conditions.