In cartilaginous bronchi, the smooth muscle is attached to the adventitial cartilage by a fibro-elastic matrix. In pigs, this matrix is stretched during muscle contraction so the inner airway wall reversibly uncouples from the outer wall. We hypothesized that inflammatory cell derived proteases may degrade this fibro-elastic matrix, increasing airway responsiveness. Airway responsiveness was determined from the sensitivity of perfused 2.0-3.5 mm id porcine bronchial segments to acetylcholine (ACh 10(-6)-10(-2)M) and from airway lumen narrowing imaged directly using a fibre-optic endoscope and video camera. Elastase (3 microliters, 1% solution) injected between the cartilage and the smooth muscle doubled sensitivity to ACh (P < 0.001) in perfused segments. Maximal airway narrowing to 10(-2) ACh was also increased from 54% to 60% (P < 0.05). Smooth muscle contraction, recorded isometrically, was not increased by elastase. We conclude that proteases may increase airway wall uncoupling in vitro, possibly by reducing the wall load, and thereby increasing responsiveness.