We evaluated changes in upper airway and lower pulmonary resistance after methacholine or ovalbumin challenge in inbred rats. Methacholine or antigen were inhaled through the intact upper airway and through a tracheostomy, in two groups of normal sensitized animals. Methacholine challenge resulted in both upper airway and lower pulmonary resistance increase regardless of the inhalation route. Lower airway ovalbumin challenge caused an increase in lower pulmonary resistance with no change in upper airway resistance. By contrast ovalbumin inhalation through the nose provoked a striking increase in upper airway resistance. Atropine pretreatment of lower airways reduced lower pulmonary response to antigen. We conclude that: 1) the increase in upper airway resistance following methacholine challenge occurs through a reflex mechanism; 2) upper airway constriction following antigen challenge through the nose results from a local mechanism; 3) the site of airway constriction depends on local mechanisms and vagal reflexes.