Coughing in response to irritation of the airways is a fundamental protective reflex that is dependent on rapidly adapting bronchopulmonary receptors and their vagal afferent fibers; reflex airway constriction, which is effected by vagomotor efferent fibers, usually accompanies coughing. Although dysfunction of vagally mediated cardiovascular and gastrointestinal reflexes is a well-documented complication of autonomic neuropathy, to date there have been no studies of the effect of peripheral autonomic failure on the cough reflex. In the study reported here, we examined the effect of acrylamide-induced neuropathy, a distal axonopathy, on the ventilatory and tracheomotor components of the cough reflex in conscious dogs. There was a reduction in the cough reflex in response to mechanical irritation of the large airways in the preclinical phase of the neuropathy, and the cough reflex was virtually abolished when the dogs had moderate neuropathy. Following withdrawal of the neurotoxin, there was a substantial recovery of the cough reflex in surviving animals. It is possible that the cough reflex may be reduced in patients with vagal neuropathy and that this might compromise protection of the airway.