The motor and inflammatory effects of capsaicin, substance P, and neurokinin A, as well as the content and release of substance P-like immunoreactivity (SP-LI), were assessed in the upper and lower guinea pig trachea and in the main bronchus. Capsaicin-induced motor and inflammatory effects were greater in the lower than in the upper tract of the trachea and much more evident at the bronchial than at the tracheal level. On the other hand, no significant regional differences were observed in the potency and efficacy of tachykinins. SP-LI content was significantly greater in the lower than in the upper tract of the trachea and about five times greater in the bronchus than in the trachea. In each single tracheal preparation, a highly significant correlation was found between the motor effect of capsaicin (but not carbachol) and the SP-LI content. Furthermore, capsaicin-induced release of SP-LI was about eight times greater in bronchial than in tracheal tissues. In view of the strict correlation observed between magnitude of motor and inflammatory actions of capsaicin (but not substance P or neurokinin A) and SP-LI content and release, it is proposed that the regional differences in the response of guinea pig respiratory tissues to activation of capsaicin-sensitive sensory fibers might be mainly prejunctional in origin.