Stimulation of pulmonary C fibre receptors by phenylbiguanide (PBG, 5-HT(3) agonist) produces hypotension, bradycardia and tachypnoea or apnoea. However, tachypnoeic or apnoeic responses are not consistent. Therefore, this study was undertaken to delineate the actions of PBG on respiration and compared with those evoked by capsaicin (TRPV1 agonist). Blood pressure, respiratory excursions and ECG were recorded in urethane anaesthetized adult rats. The effect of PBG or capsaicin was evaluated before and after ondansetron (5-HT(3) antagonist), capsazepine (TRPV1 antagonist) or bilateral vagotomy. In addition, their effect on vagal afferent activity was also evaluated. Bolus injection of PBG produced concentration-dependent (0.1-100 microg kg(-1)) hypotensive and bradycardiac responses, while there was tachypnoea at lower concentrations (0.1-3 microg kg(-1)) and apnoea at higher concentrations (10-100 microg kg(-1)). After vagotomy or after exposure to ondansetron both tachypnoeic and apnoeic responses were abolished along with cardiovascular responses. However, capsazepine (3 mg kg(-1)) did not block the PBG-induced reflex responses. Capsaicin (0.1-10 microg kg(-1)), on the other hand, produced a concentration-dependent apnoea, hypotension and bradycardia but tachypnoea was not observed. Ondansetron failed to block the capsaicin-induced reflex response while bilateral vagotomy abolished bradycardiac and hypotensive responses and attenuated the apnoeic response. In another series, vagal afferent activity and cardio-respiratory changes evoked by PBG were blocked by ondansetron. However, capsaicin failed to activate the PBG-sensitive vagal afferents even though cardio-respiratory alterations were observed. The present observations indicate that PBG produced tachypnoea at a lower concentration and apnoea at a higher concentration involving vagal afferents which are different from those excited by capsaicin.