We describe a persistent increase in nonspecific bronchial responsiveness following acute exposure to strong respiratory irritants in four subjects with no past history of asthma or atopy and in a subject with mild asthma. They were exposed either to a bleaching agent, sulfuric acid, hydrochloric acid, perchloroethylene, or toluene diisocyanate fumes. In all cases the inhalation of high concentrations of irritant fumes was brief (less than one hour) and induced acute symptoms of cough and dyspnea. The asthmatic subject developed a severe bronchospasm which required mechanical ventilation. In all subjects the exposure led to prolonged (more than one year) symptoms of variable airflow obstruction induced on contact with common respiratory irritants. In the previously normal subjects, a mild hyperresponsiveness to methacholine could be observed. The asthmatic subject became dependent on steroids. No change in the forced expiratory volume in one second was observed when the subject exposed to sulfuric acid was rechallenged in the laboratory, but her nonspecific bronchial responsiveness was then back to normal at this time. When those exposed to perchloroethylene or toluene diisocyanate fumes were reexposed to these agents, a late asthmatic response occurred, suggesting that the subjects developed occupational asthma after an intense short-term exposure to perchloroethylene or toluene diisocyanate. We conclude that airway hyperresponsiveness can develop or increase after the inhalation of high concentrations of irritants and that these changes may be prolonged. Occupational asthma following intense short-term exposure to sensitizing agents should be differentiated from airway hyperresponsiveness which results from a nonsensitizing mechanism, as in the reactive airway dysfunction syndrome.