Epiglottic dysfunction due to environmental exposure is a well-known entity. The most common causes of epiglottic dysfunction include trauma (thermal, chemical, and blunt), infection, allergy, neoplasm, and neurologic disorders. We report an unusual case of epiglottic dysfunction due to isocyanate inhalation exposure and review the literature concerning this subject. Following inhalation exposure to diphenylmethane diisocyanate, our patient developed persistent repeated airway obstruction during inspiration. Fiberoptic rhinolaryngoscopy showed that the epiglottis obstructed the glottic airway during each inspiratory cycle. The epiglottic dysfunction was also well demonstrated by barium contrast cineradiography. Total epiglottectomy resulted in resolution of the patient's upper airway obstructive symptoms. Histologically, marked inflammatory changes of the epiglottis were noted, including a focal infiltrative pattern, focal fibrosis, edema, and reactive changes.