Obstructive sleep apnea (OSA) is characterized by repetitive nocturnal upper airway obstructions that are associated with sleep disruption and cyclic intermittent hypoxia (CIH) The cyclic oscillations in oxygen saturation are thought to contribute to cardiovascular and other morbidity but animal and patient studies of the pathogenic link between CIH and these diseases have been complicated by species differences and by the effects of confounding factors such as obesity, hypertension, and impaired glucose metabolism. To minimize these limitations we set up a model of nocturnal CIH in healthy humans. We delivered oxygen for 15 seconds every 2 minutes during sleep while subjects breathed 13% oxygen in a hypoxic tent to create 30 cycles/hour of cyclic desaturation-reoxygenation (SpO₂ range 95 - 85%). We exposed subjects overnight for 8-9 hours/day for two (10 subjects) and four weeks (8 subjects). The CIH exposure induced respiratory disturbances (central apnea hypopnea index: 3.0±1.9 to 31.1±9.6 per hour of sleep at 2 weeks). Exposure to CIH for 14 days induced an increase in slopes of hypoxic and hypercapnic ventilatory response (1.5±0.6 to 3.1±1.2 L.min^-1.% drop in SpO₂ and 2.2 ± 1.0 to 3.3±0.9 L.min^-1.mmHg CO₂^-1 respectively) consistent with hypoxic acclimatization. Waking normoxic arterial pressure increased significantly at 2 weeks for systolic (114±2 to 122±2 mmHg) and for diastolic at 4 weeks (71±1.3 to 74±1.7 mmHg). We propose this model as a new technique to study the cardiovascular and metabolic consequences of CIH in human volunteers.