This chapter reviews the evidence that identifies the types and anatomic locations of tachykinins in the airways, the factors that release these substances, and the effects. It considers the evidence that different forms of inflammation can change neutral endopeptidase (NEP)-like activity in the airways, the mechanisms by which these changes might occur, and the importance of other peptidases that may become relevant when the activity of NEP is diminished. When the relaxant effects of the expected products of vasoactive intestinal peptide (VIP) hydrolysis were studied in a tracheally perfused lung model, the hydrolysis products had markedly less activity than intact VIP. Comparison of VIP hydrolysis fragments from normal lungs indicates that NEP and mast cell tryptase inactivate VIP, while only tryptase fragments are present in the perfusate of inflamed lungs. The physiological effects of neuropeptides in the lung are receptor-mediated events that depend on the apposition of ligand and receptor.