Experiments were conducted with chloralose-urethan anesthetized rats to assess the effects of 1) bilateral stimulation of the cervical vagus nerves and 2) parasympathomimetic and sympathomimetic agents. Transpulmonary pressure (Ptp) was used as an index of airway smooth muscle tone, and peak inspiratory Ptp (Ptppeak) values were used for a comparison of responses. In untreated animals, vagal stimulation elicited an increase in Ptppeak of 155%. Cooling of the vagus nerves to 15 degrees C abolished the response of Ptppeak to vagal stimulation. Although isoproterenol (1-10 micrograms/kg i.v.) did not alter resting Ptppeak, it did prevent vagal stimulation from evoking an increase in Ptppeak. Nadolol (1.5 mg/kg i.v.) augmented the increase in Ptppeak elicited by vagal stimulation. Vagal stimulation did not evoke any change in Ptppeak after the administration of both nadolol and atropine or after combined administration of nadolol, atropine, and either serotonin aerosol or prostaglandin F2 alpha. In rats pretreated with capsaicin 1 wk before the experiment, vagal stimulation evoked an increase in Ptppeak that was not statistically different from that of untreated control animals. Therefore, nonadrenergic noncholinergic systems did not appear to play an independent role in the response of the airways to the activation of the vagus nerves.