Recurrent and intermittent nocturnal hypoxia is characteristic of several diseases including chronic obstructive pulmonary disease, congestive heart failure, obesity-hypoventilation syndrome and obstructive sleep apnea. The contribution of hypoxia to cardiovascular morbidity and mortality in these disease states is unclear, however. To investigate the impact of recurrent nocturnal hypoxia on hemodynamics, sympathetic activity, and vascular tone we evaluated 10 normal volunteers before and after 14 nights of nocturnal sustained hypoxia (mean oxygen saturation 84.2%, 9 hours per night). Over the exposure, subjects exhibited ventilatory acclimatization to hypoxia as evidenced by an increase in resting ventilation (PaCO2 41.8 ± 1.5 vs 37.5± 1.3 mmHg; mean ± SD; p<0.05) and of the isocapnic hypoxic ventilatory response (slope 0.49 ± 0.1 vs 1.32 ± 0.2 l/min/1% fall in saturation; p<0.05). Subjects exhibited a significant increase in mean arterial pressure (86.7 ± 6.1 vs. 90.5 ± 7.6, p<0.001), muscle sympathetic nerve activity (20.8 ± 2.8 vs 28.2 ± 3.3 bursts/min; p<0.01) and forearm vascular resistance (39.6 ± 3.5 vs 47.5 ± 4.8 mmHg/ml/100g tissue/min; P<0.05). Forearm blood flow during acute isocapnic hypoxia was increased after exposure but during selective brachial intra-arterial vascular infusion of the alpha-blocker phentolamine was unchanged after exposure. Finally, there was a decrease in reactive hyperemia to 15 min of forearm ischemia following the hypoxic exposure. Recurrent nocturnal hypoxia thus increases sympathetic activity and alters peripheral vascular tone. These changes may contribute to the increased cardiovascular and cerebrovascular risk associated with clinical diseases that are associated with chronic recurrent hypoxia.