Reactive airways dysfunction syndrome (RADS) is an asthma-like condition that follows exposure to very high concentrations of an irritant material. We assessed the time-course of pathophysiological alterations in a model of RADS. Sprague-Dawley rats were exposed to 1,500 parts per million (ppm) of chlorine for 5 min. Lung resistance (RL), responsiveness to inhaled methacholine (MCh), the airway epithelium and bronchoalveolar lavage (BAL) were assessed over a 3 month period after exposure. RL increased significantly up to 3 days after exposure, reaching a maximal change of 110+/-16% from baseline. There was a significant decrease in the concentration of MCh required to increase RL by 0.20 cmH2O x mL(-1) x s from days 1-7 after exposure. In some rats, MCh hyperresponsiveness and RL changes persisted after exposure for as long as 1 and 3 months, respectively. Histological evaluation with morphometric evaluation revealed epithelial flattening, necrosis, increase in smooth muscle mass and evidence of epithelial regeneration. BAL showed an increased number of neutrophils. The timing of maximal abnormality in the appearance of the epithelium (days 1-3) corresponded to that of the maximal functional changes. Acute high chlorine exposure results in functional and pathological abnormalities that resolve in the majority of animals after a variable period; however, these changes can persist in some animals. Functional abnormalities in the initial stages may be related to airway epithelial damage.