Purpose of the Study. Airway hyper-responsiveness is a consistent observation seen in asthmatic patients. In asthma, inflammatory cellular influx and mediator release results in epithelial damage, vascular leak, and alterations in mucus production and secretion. Studies suggest that C-fibers which innervate airway epithelium may be more densely packed with substance P in asthmatic patients than in normal subjects. Damage to the epithelium may increase stimulation of the C-fibers and subsequent tachykinin release including substance P. Tachykinins are metabolized by neutral endopeptidase (NEP) which are found in airway epithelium and smooth muscle. Airway damage may cause enhanced tachykinin-induced effect. The purpose of this study was to investigate the inter-relationship between tachykinins and reduced NEP on the effects of pulmonary functions as well as bronchoalveolar lavage findings. Methods. Guinea pigs were given an aerosolized solution of acrolein, a component of cigarette smoke and smog, which is known to cause epithelial cytotoxicity and increased sensitivity to acetylcholine. Pulmonary functions were measured via body box. Dose response curves were calculated from subject guinea pigs given the acrolein as well as the control group following substance P administration. Subsequently, subject as well as control guinea pigs were exposed to thiorphan to inhibit NEP. They were then given subsequent challenges of either IV or aerosolized substance P and pulmonary testing as well as bronchoalveolar lavage was performed. NEP activity was measured at 1, 7, and 28 days after exposure. Results. Pulmonary intonation and epithelial damage were prominent on the day after acrolein exposure showing influx of monocytes, neutrophils, and epithelial damage.