Peribronchial edema has been proposed as a mechanism enhancing airway responses to constrictor stimuli. Acute exposure to altitude in nonacclimatized lowlanders leads to subclinical interstitial pulmonary edema that lasts for several days after ascent, as suggested by changes in lung mechanics. We, therefore, investigated whether changes in lung mechanics consistent with fluid accumulation at high altitude within the lungs are associated with changes in airway responses to methacholine or exercise. Fourteen healthy subjects were studied at 4,559 and at 120 m above sea level. At high altitude, both static and dynamic lung compliances and respiratory reactance at 5 Hz significantly decreased, suggestive of interstitial pulmonary edema. Resting minute ventilation significantly increased by approximately 30%. Compared with sea level, inhalation of methacholine at high altitude caused a similar reduction of partial forced expiratory flow but less reduction of maximal forced expiratory flow, less increments of pulmonary resistance and respiratory resistance at 5 Hz, and similar effects of deep breath on pulmonary and respiratory resistance. During maximal incremental exercise at high altitude, partial forced expiratory flow gradually increased with the increase in minute ventilation similarly to sea level but both achieved higher values at peak exercise. In conclusion, airway responsiveness to methacholine at high altitude is well preserved despite the occurrence of interstitial pulmonary edema. We suggest that this may be the result of the increase in resting minute ventilation opposing the effects and/or the development of airway smooth muscle force, reduced gas density, and well preserved airway-to-parenchyma interdependence.