The sleep apnea/hypopnea syndrome (SAHS) affects 1-4% of the middle-aged population and is caused by repeated occlusion of the upper airway mainly at the retropalatal level. It is unclear why SAHS patients obstruct their upper airways during sleep while others do not. We hypothesized that upper airway dilator muscle function may be impaired in SAHS patients and that chronic CPAP therapy may enhance upper airway function. We, therefore, examined the effects of upper airway negative pressure on reflex palatal muscle activity in 16 normal nonsnoring awake male subjects and 16 awake SAHS patients using electromyography. The application of negative upper airway pressure (0 to -12.5 cm H2O) caused increases in levator palatini (LP, p < 0.001) and palatoglossus (PG, p < 0.001) activity, 100 msec after pressure stimulus in normal subjects. Application of upper airway negative pressure in SAHS patients caused an increase in LP activity (p < 0.05) but not in PG activity. Reflex electromyographic response to negative pressure was reduced in SAHS patients compared to normal subjects for both muscles (p < 0.001). When the seven thinnest SAHS patients were compared with seven normal subjects matched for BMI and age, the SAHS patients still demonstrated impaired responses to negative pressure for both muscles (p < 0.001). A further eight SAHS patients were studied either while concurrently taking nightly CPAP therapy and also off CPAP (at least 3 nights). Chronic nightly CPAP therapy improved the reflex response of both LP (p < 0.001) and PG (p = 0.003) to nasal negative pressure application. Thus, untreated SAHS patients have impaired electromyographic responses to negative upper airway pressure suggesting impaired defence of the upper airway, which is improved by nightly CPAP therapy.