It is now recognized that acute inhalational exposure to irritant gases such as chlorine can cause an asthma-like abnormality known as reactive airways dysfunction syndrome (RADS). The aim of this study was to evaluate the effects of exposure to various levels of chlorine on airway mucosa and lung parenchyma in an attempt to develop an animal model of this syndrome. Seventy-four Sprague-Dawley rats were exposed to air (controls) or to 50, 100, 200, 500, and 1500 ppm of chlorine for 2 to 10 min. Histological assessment was performed at 1, 3, 6, 12, 24, and 72 h after exposure. The results show that exposure to low concentrations (500 ppm) did not induce significant histological changes. Exposure to 1500 ppm for 2 min induced perivascular edema and the appearance of focal mild inflammation, whereas exposure to the same concentration for 10 min caused profound histological changes, including (1) 1 h: airspace and interstitial edema associated with bronchial epithelial sloughing; (2) 6 to 24 h: decreased edema and the appearance of mucosal polymorphonuclear leukocytes, maximal at 12 h; (3) 72 h: epithelial regeneration, manifested by hyperplasia and goblet cell metaplasia. We conclude that acute exposure to chlorine at a concentration of 1500 ppm for 10 min induces significant airway mucosal abnormalities that vary over a short period of time. Whether these abnormalities are related to the subsequent development of RADS awaits further experiments.