Individuals with obstructive sleep apnea syndrome (OSAS) are at high risk for cardiovascular morbidity and mortality. The effects of OSAS severity and nocturnal continuous positive airway pressure (CPAP) on daytime baroreflex sensitivity (BRS) and nitric oxide (NO) production were investigated in OSAS patients. Fifty-one consecutive males with OSAS and 29 age-matched healthy men underwent the Valsalva test and standard polysomnography. Patients with an apnea-hypopnea index (AHI) of >or=20 episodes per hour were randomized to receive CPAP treatment for 3 months (n=14) or no such treatment (n=19). The BRS index measured from the overshoot phase (phase IV) of the Valsalva maneuver and plasma NO concentration were significantly lower, whereas the AHI, oxygen desaturation time, arousal index, percentage of sleep stage 1, and systolic blood pressure were significantly greater, in patients with an AHI of >or=20/h than in those with an AHI of <20/h or in controls. The 24-h urinary excretion of norepinephrine was significantly reduced and the plasma NO concentration was significantly increased after one night of CPAP. The BRS index for phase IV and the Valsalva ratio were significantly increased in the CPAP group after the 3-month treatment period but remained unchanged in the non-CPAP group of OSAS patients. The daytime BRS index and NO production were thus inversely related to the severity of OSAS, and successful CPAP treatment improved these parameters in patients with moderate to severe OSAS. CPAP may therefore reduce the risk of cardiovascular complications due to endothelial dysfunction or increased sympathetic activity.