Deformation of the upper airway (UA) by negative transmural pressure alters the activity of UA mechanoreceptors causing a reflex increase in UA muscle activity. Topical anesthesia of the UA mucosa, which greatly reduces this reflex response, causes an increase in upper airway resistance during stage 2 sleep. We hypothesized that topical anesthesia of the UA mucosa would predispose to UA instability at sleep onset, and therefore examined the effect of UA anesthesia on pharyngeal resistance (Rph) in stage 1 sleep. Eleven normal healthy volunteers were instrumented to record standard polysomnographic variables, respiratory airflow, and UA pressure at the nasal choanae and the epiglottis. Subjects were permitted to sleep until stable stage 2 sleep was reached and were then awoken. This procedure was repeated three times to obtain reproducible wake-sleep transitions. The UA mucosa was then anesthetized with 10% lidocaine to the oropharynx and laryngopharynx, and the pharyngeal mechanics studied during the subsequent wake-sleep transition. 3 subjects were excluded because of failure to resume sleep post-anesthesia. Rph was significantly higher after anesthesia during stage 1 sleep [2.88 (0.77) cmH₂O/L/s; mean (SEM)] compared to control [0.95 (0.35) cmH₂O/L/s; P<0.05] but there was no difference during wakefulness. Furthermore, there was a significant rise in Rph at wake to sleep transitions and a significant fall in Rph at sleep to wake transitions after anesthesia (P<0.05) but not in the control condition. We conclude that sensory receptors in the UA mucosa contribute to the maintenance of UA patency at wake-sleep transition in normal humans.