Recently, it has been suggested that the peripheral vagal nerve might participate in the bronchoconstriction locally in addition to the concept of "vagal reflex". We investigated the contribution of the vagal nerve on the modulation of airway responses to histamine (8 micrograms/kg, iv) in anesthetized and mechanically ventilated guinea-pigs. Airway responses were assessed by measurement of pulmonary resistance (RL). To determine whether the vagal nerve mediates excitatory effects by "vagal reflex" in guinea-pigs, we investigated the effects of vagotomy or hexamethonium (2 mg/kg, iv). Increase in RL induced by histamine was significantly enhanced after the vagotomy or the treatment of hexamethonium. Histamine-induced bronchoconstriction was also enhanced by the vagotomy in the animals after the administration of propranolol (1 mg/kg, iv). To determine whether the peripheral vagal nerve may play any role in the vagotomized animals, we investigated the effect of atropine (1 mg/kg, iv). Atropine reduced histamine-induced bronchoconstriction significantly in the vagotomized guinea-pigs or in the animals treated with hexamethonium. We conclude that the vagal nerve mainly exerts on inhibitory role through the central nervous system, and that the peripheral vagal nerve distal to ganglion plays an excitatory effects by releasing acetylcholine from the terminals in histamine-induced bronchoconstriction in guinea-pigs.