Seven beagles were exposed via a tracheostomy to smoke from 10 cigarettes/day, 5 days/wk for 10 months; 2 other dogs were exposed for 6 months only. Four dogs served as sham-exposed control animals. Mucus was collected 2 times/wk prior to and during the exposure period by resting a cytology brush on the lower trachea for 2 to 5 min. At least once prior to and as often as 3 times during exposure, transpulmonary pressure and flow were monitored under anesthesia to determine resistance RL. Two airway responses to methacholine were determined: the infusion response delta Ri, the increment in RL 4 to 6 min after infusion of 4 micrograms/kg/min, and the aerosol response delta Ra, the increment in RL 2 min after aerosolization of 2 mg/ml, the highest common dose reached. Eight of 9 smoking dogs developed persistent mucus hypersecretion. In 5 dogs, tracheal mucus flux increased 5- to 10-fold; in 3 dogs, the increase was 2 to 3 times that of control animals. One of the sham-exposed dogs developed moderate hypersecretion. After 10 months of smoke exposure, delta Ri increased to 2.24 times that of the initial value (+/- 0.47 SE) (n = 7, p less than 0.05), whereas delta Ra decreased to 0.28 times that of the control value (+/- 0.21 SE) (n = 6, p less than 0.02). The difference between aerosol and infusion response, delta Rai = delta Ra - delta Ri, is an index of relative hyporesponsiveness to methacholine aerosol.(ABSTRACT TRUNCATED AT 250 WORDS)