The present experiments were performed to investigate whether neurogenic inflammation in rat trachea (with edema formation and protein extravasation when the circulation is intact) induced by electrical field stimulation of neuropeptide-containing C fibers in the vagal nerve is accompanied by increased negativity of interstitial fluid pressure (Pif). Increased negativity of Pif in the trachea occurs in dextran anaphylaxis and mast cell degranulation and facilitates edema formation under these circumstances. Experiments were performed after circulatory arrest had been induced in pentobarbital anesthesia to prevent edema formation, which will raise Pif and potentially cause underestimation of an increased negativity of Pif. After induction of circulatory arrest, the vagal nerve was isolated and placed in a stimulating electrode. The trachea was then exposed and covered with mineral oil, and measurement of Pif was started as soon as possible thereafter. Pif was measured with sharpened glass capillaries (tip diameter, 3 to 7,um) connected to a servocontrolled counterpressure system. Pif in the control group (n=12) did not change throughout the observation period. Electrical stimulation of the left vagal nerve caused Pif to fall in all experiments, from −1.1±1.1 mm Hg in the control condition to an average of −10.6±3.4 mm Hg (n=9, P<.01). In some experiments, a continuous recording of Pif was obtained, showing that the reduction of Pif started within 30 seconds after onset of stimulation to reach and later remain at a stable level within a few minutes. The experimental protocol was repeated after the C fibers had been nearly depleted of neuropeptides with capsaicin. In this group (n=7), vagal nerve stimulation had no effect on Pif, which averaged −0.89±0.9 and −0.08±1.7 mm Hg before and after stimulation, respectively (P>.05). Mast cell degranulation with C48/80 (n=5) and polymyxin B (n=6) resulted in Pif of −5 to −6 mm Hg, and subsequent vagal nerve stimulation was without effect on Pif. This could suggest that the increased negativity of Pif occurring in the initial phase of neurogenic inflammation in rat trachea involves mast cell degranulation. Finally, the presence and localization of immunoreactive calcitonin gene-related peptide (CGRP) and substance P were studied in transverse sections of trachea. Normally, the neuropeptides were typically located right under the mucosa, adjacent to mast cells and blood vessels. Capsaicin resulted in near depletion of immunoreactive calcitonin gene-related peptide and substance P. In conclusion, electrical field stimulation of the vagal C fibers in rat trachea for the first time provides experimental evidence for a functional innervation of loose connective tissue, causing increased negativity of Pif.