Experiments were performed to assess the effects of chronic hypoxia on systemic vasoreactivity in conscious unrestrained rats and in abdominal aortic rings. Two groups of rats were used: normoxic controls and chronically hypoxic rats that were maintained in a hypobaric chamber (380 mmHg) for 4 wk before experimentation. In conscious animals instrumented with pulsed Doppler cardiac output probes and arterial and venous catheters, mean arterial pressure and mean cardiac output were measured before and during graded continuous infusions of phenylephrine (PE), angiotensin II, and arginine vasopressin (AVP). Measurements were made while the animals breathed either room air or 12% O2. Acute exposure to 12% O2 significantly reduced pressor and vasoconstrictor responses for all three agents. These responses were also attenuated in the chronically hypoxic rats in 12% O2; however, acute return to room air conditions did not return pressor or vasoconstrictor responses to normoxic control levels. In abdominal aortic rings from both groups of animals, cumulative dose-response curves to PE and AVP were completed in 21 and 3% O2 conditions. Neither acute nor chronic hypoxia caused a shift in the dose-response curves. In rings from control rats, maximum tension responses to AVP were significantly diminished in 3% O2. Rings from chronically hypoxic rats exhibited less maximum tension to AVP in 21% O2 than did rings from control rats. We conclude that acute hypoxia reversibly attenuates systemic vasoreactivity and that chronic hypoxia induces a more sustained decrease in reactivity. In addition, at least part of the mechanism may reside within the vasculature.