The afferent pathway of an upper airway reflex in which genioglossus muscle electromyographic (GG EMG) activity is influenced by pharyngeal pressure changes was investigated in 20 anesthetized rabbits. We took advantage of the fact that the upper airway was separated into two compartments by pharyngeal closure occurring when the animals breathe through a tracheostomy. This allowed pressure to be delivered selectively either to the nose and nasopharynx or to the larynx and hypopharynx. Midcervical vagotomy did not eliminate the GG EMG response to pressure stimuli. On the other hand high cervical vagotomy or superior laryngeal nerve section eliminated the response in the laryngeal compartment, but not in the nasopharyngeal compartment. Topical anesthesia of the mucosa of the nose, pharynx, and larynx abolished the response in both compartments. Therefore we conclude that more than one afferent pathway exists for this upper airway pressure reflex; the primary afferent pathway from the laryngeal compartment is the superior laryngeal branch of the vagus nerve, whereas the primary afferent pathway for the nasopharynx is nonvagal. Trigeminal nerve, glossopharyngeal nerve, and/or nervus intermedius carry nonvagal afferents from the nasopharynx and nose. The topical anesthetic and nerve section studies suggest that superficial receptors mediate this response. The occurrence of swallowing in response to upper airway pressure changes and its elimination by topical anesthesia or superior mechanoreceptors may mediate both genioglossus respiratory responses and swallowing responses.