We investigated whether the airway constrictive response to stimulation of bronchopulmonary C-fiber afferents is altered during the maturation process. Isometric tension was measured in airway rings isolated from three tracheobronchial locations (intrathoracic trachea, main and hilar bronchi) and compared between mature (M) (407 ± 10 g; mean ± SEM, n=36) and immature (IM) (161 ± 5 g, n=35) guinea pigs. Our results showed no difference in the acetylcholine (ACh, 10^-5 M)- or KCl (40 mM)-induced contraction between M and IM groups, regardless of the airway location. In sharp contrast, the concentration-response curves of capsaicin (10^-8 -10^-6 M) were distinctly lower in IM hilar bronchi; for example, response to the same concentration of capsaicin (10^-6 M) was 89.2 ± 15.3% of that of ACh (10^-5 M) in IM and 284.7 ± 43.2% in M animals. Similar but smaller differences in the bronchoconstrictive response to capsaicin between IM and M groups were also observed in trachea and main bronchi. Electrical field stimulation (EFS) induced airway constriction in all three locations in both M and IM groups. However, after administration of atropine (10^-6 M) and propranolol (10^-6 M), the EFS-induced contraction in hilar bronchi of IM animals was significantly smaller than that in M animals, and this difference was not prevented by a pretreatment with indomethacin (5x10^-5 M). Although radioimmunoassay showed no difference in the tissue content of substance P (SP) between M and IM airways, the constrictive responses to both exogenous SP and neurokinin A were markedly greater in M airways at all three locations. In conclusion, the constriction of isolated airways evoked by C-fiber stimulation was significantly weaker in the IM guinea pigs, probably due to a less potent effect of tachykinins on the airway smooth muscle.