Exercise-induced asthma, as recognized in asthmatic subjects, is an exaggerated airway response to airway dehydration in the presence of inflammatory cells and their mediators. The airway narrowing is primarily caused by contraction of bronchial smooth muscle. The milder airway narrowing documented in response to exercise in elite athletes and otherwise healthy subjects may simply be the result of the physiologic responses and pathologic changes in airway cells arising from dehydration injury. These changes, which include excessive mucus production and airway edema, would serve both to cause cough and to amplify the narrowing effects of normal bronchial smooth muscle contraction, resulting in symptoms. These changes are more likely to occur in healthy subjects who exercise intensely for long periods of time breathing cold air, dry air, or both. Under these conditions, the ability to humidify inspired air may be overwhelmed, causing significant dehydration of the airway mucosa and an increase in osmolarity, even in small airways. In addition to dehydration injury, airway narrowing to pharmacologic and physical agents may occur as a result of injury caused by large volumes of air containing irritant gases, particulate matter, or allergens being inspired during exercise. As a result, the airways may become inflamed, and the airway smooth muscle may become more sensitive. These events could result in the same exaggerated airway response to dehydration, as documented in asthmatic subjects. (J Allergy Clin Immunol 2000;106:419-28.)