Airway hyperresponsiveness to histamine is a hallmark of asthma, and histamine inhalation reproduces asthma symptoms. Plasma histamine concentrations are elevated during the early and late responses to inhaled allergens, and may also increase during spontaneous acute asthma episodes. Ordinary doses of currently available antihistamines (H1-receptor antagonists) have minimal bronchodilator and bronchoprotective activity. In severe persistent asthma, H1 antagonists have no significant clinical effect. In moderate persistent asthma, clinical benefits of H1 antagonists are apparent, but may not be worth the potential risks of the higher-than-usual doses required. When mild seasonal asthma and allergic rhinitis coexist, however, relief of rhinitis symptoms with H1 antagonists administered in ordinary dose is associated with significant improvement in asthma symptoms.