Since substance P (SP)-like immunoreactivity has been demonstrated in vagal sensory fibres of bronchopulmonary origin, it was considered of interest to (1) characterize the pattern of responses to SP injected into the pulmonary as well as the systemic arterial system, and (2) assess the types of vagal afferents that are affected by SP. Experiments were performed on 15 pentobarbital-anaesthetized, spontaneously breathing rabbits. Efferent phrenic nerve activity was monitored as an index of central respiratory neural output. Intra-atrial injections of SP into the pulmonary circulation (100 ng kg-1) increased the respiratory rate, and peak integrated phrenic amplitude by 47 +/- 8 and 40 +/- 4%, respectively, above the controls. In addition, SP elicited augmented breaths (ABs) within 2-3 s in 67% of the trials. In contrast to right atrial injections, no ABs and no significant changes in respiratory rate were observed in response to intra-aortic injections of SP (100 ng kg-1). Tidal phrenic activity rise after aortic injections of SP was significantly less as compared with right atrial administrations of SP. Since both routes of administration decreased the arterial blood pressure to the same extent, these respiratory responses were not likely secondary to cardiovascular changes. After administration of an SP antagonist (D-Arg-D-Trp7,9, Leu11, SP), respiratory responses to SP were significantly attenuated. Also, the rate of occurrence of ABs elicited by releasing the tracheal occlusions was reduced (control 95 vs. 14% SP antagonist). Bilateral vagotomy abolished the tachypnoeic response and reduced the magnitude of the phrenic nerve increments caused by right atrial injection of SP.(ABSTRACT TRUNCATED AT 250 WORDS)