To investigate a possible role of a nonadrenergic inhibitory nervous system in airway hyperreactivity, we measured changes in RL and CL caused by electrical stimulation of cervical vagus nerve during the infusion of 5-HT, after treatment with atropine and propranolol in 18 cats. RL decreased to 56 +/- 3% (mean +/- SE) and CL increased to 186 +/- 13% of the prestimulated values, respectively, after stimulation. Hexamethonium diminished these responses significantly. Airway reactivity to 5-HT was reduced by continuous electrical stimulation of cervical vagus nerve in cats pretreated with atropine and propranolol. Hexamethonium potentiated airway reactivity to 5-HT. These results suggest that a nonadrenergic inhibitory nervous system could play an important role in the control of the bronchomotor tone and contribute to airway hyperreactivity.