Hemodynamics, muscle sympathetic nerve activity (MSNA) and forearm blood flow (FBF) were evaluated in 12 normal subjects before, during (1 hour and 7 hours) and after ventilatory acclimatization to hypoxia achieved with 8 hours of continuous poikilocapnic hypoxia. All results are mean ± standard deviation. Subjects experienced mean oxygen saturation (SpO2) of 84.3 ± 2.3 % during exposure. The exposure resulted in hypoxic acclimatization as suggested by end-tidal CO2 (EtCO₂ 44.7 ± 2.7 [pre] vs. 39.5 ± 2.2 mmHg [post], p<0.001) and by ventilatory response to hypoxia (1.2 ± 0.8 [pre] vs. 2.3 ± 1.3 l/min/1% fall in saturation [post], p<0.05). Subjects exhibited a significant increase in heart rate across the exposure that remained elevated even upon return to room air breathing compared to pre exposure (67.3± 15.9 vs. 59.8± 12.1 hb/min p<0.008). Although arterial pressure exhibited a trend toward an increase across the exposure, this did not reach significance. MSNA initially increased from room air to poikilocapnic hypoxia (26.2 ± 10.3 to 32.0 ± 10.3 burst/100hb NS @ 1 hour of exposure), however, MSNA then decreased below the normoxic baseline despite continued poikilocapnic hypoxia (20.9 ± 8.0 burst/100hb, 7 hr. Hx vs. 1 hr Hx; p<0.008 @ 7 hours). MSNA decreased further after subjects returned to room air (16.6 ± 6.0 burst/100hb p<0.008 compared to baseline). Forearm conductance increased after exposure from 2.9 ± 1.5 to 4.3 ± 1.6 (conductance units) (p<0.01). These findings indicate alterations of cardiovascular and respiratory control following 8-hours of sustained hypoxia producing acclimatization but sympathoinhibition.