The sensory receptors and reflex pathways of the nonadrenergic inhibitory nervous system (NAINS) were examined, using separately ventilated left and right lungs in cats. During bronchoconstriction induced by 5-hydroxytryptamine (5-HT) (50 to 250 micrograms/kg/min, i.v.) infusion after atropine (3 mg/kg, i.v.) and propranolol (2 mg/kg, i.v.), one lung was challenged with (1) citric acid aerosol or (2) capsaicin aerosol or (3) lung volume change (lung inflation). Citric acid or capsaicin inhalation to one lung produced significant bronchodilatation in not only the stimulated lung (SL) but also in the opposite lung (OL). The 5-HT-induced change in pulmonary resistance (RL) was reduced 66.5 +/- 3.3% (mean +/- 1 SE) (SL) and 53.0 +/- 8.1% (OL) by citric acid (20%) and 40.5 +/- 8.9% (SL) and 44.0 +/- 9.9% (OL) by capsaicin (0.1%) inhalation, respectively. These bronchodilatations were abolished by bilateral vagotomy. Inflation of one side of the lung did not reduce the 5-HT-induced change in RL in the OL. These findings indicate that (1) C-fiber and irritant receptors are the possible sensory receptors of the NAINS reflex pathway, and (2) afferent nerve stimulation of NAINS in one lung can produce reflex bronchodilatation in both lungs.