Preclinical studies suggest that the endocannabinoid anandamide restrains allergic airway obstruction and inflammation. Therefore, we applied saline or allergens via bronchoscopy into different lung segments of patients with allergic asthma. Twenty-four hours later, anandamide concentrations in bronchoalveolar lavage fluids had increased more than fourfold. Anandamide concentrations correlated with severity of airway inflammation. These observations suggest that allergen exposure specifically activates the pulmonary endocannabinoid system (ECS) in patients with allergic asthma.