Intratracheal administration of purified Pseudomonas aeruginosa exoenzyme S elicited extensive, grossly observable damage in the rat lung within 2 h. Light and electronmicroscopy revealed injury and necrosis of bronchial epithelium, type I pneumocytes and capillary endothelial cells after 1 h; associated haemorrhage, fibrinous exudation and released type II cell lamellar bodies in alveolar lumina after 1-12 h; progressively increasing accumulations of polymorphonuclear leucocytes in the bronchi and alveoli and in alveolar septae (interstitial pneumonia) after 1-12 h; collapse of alveolar septal connective tissue and damage to pulmonary arterioles and venules. Treatment of monolayer cultures of bronchial fibroblasts with purified exoenzyme S elicited vacuolation of the cells with apparent membrane damage as revealed by light and electronmicroscopy. In-vivo production and activity of P. aeruginosa exoenzyme S may be an important pathogenicity determinant in the necrotising lung injury characteristic of P. aeruginosa pneumonia.