The influence of lung volume on bronchopulmonary reactivity was investigated in 4 groups of 14 anaesthetized paralysed mechanically ventilated guinea-pigs: animals of group 1 served as control; in animals of group 2, the parasympathetic nervous system was blockaded with atropine; animals of group 3 were submitted to a bilateral cervical vagotomy; animals of group 4 were both vagotomized and pretreated with atropine. In each group, the animals were randomly divided into 2 subgroups: one was ventilated at zero end-expiratory pressure (ZEEP), the other with 0.2 kPa positive end-expiratory pressure (PEEP) resulting in a mean increase in lung volume of about 1 ml. Bronchopulmonary response to infused histamine was assessed by the respiratory conductance and compliance values measured during bronchoconstriction (respectively HGrs and HCrs). In the control group, animals exposed to PEEP were found significantly less reactive than those ventilated at ZEEP. In groups 2, 3 and 4, this difference was significantly reduced for HGrs and even abolished for HCrs. These results demonstrate that the effect of lung volume on moderate histamine-induced bronchoconstriction in guinea-pigs is not purely mechanical, but is partly vagally mediated. They also suggest that this vagally mediated inhibitory influence results from involvement of central reflexes evoked by stretch receptor stimulation.