To examine the baroreflex response in humans during and immediately after acute hypoxia exposure, the cardiac baroreflex sensitivity (BRS) was studied using adaptation of RR intervals in response to spontaneous systolic blood pressure fluctuations (sequences methodology) in 11 unacclimatized subjects. All measurements were made under fixed breathing rate, and realized consecutively at baseline level (20 min), at an inspired oxygen concentration of 11% (15 min) and again under normoxic conditions (20 min; recovery period). The spontaneous baroreflex response decreases progressively during hypoxic exposure, causing a tachycardic response at this FiO2 without any significant alteration of the systolic or diastolic blood pressure. The magnitude of decrease for this variable at the end of exposure averaged 42.9 +/- 15.6%. The simultaneous spectral analysis of heart rate (HR) variability in hypoxic condition confirmed an alteration in the parasympathetic activity (HFnu: -17.8 +/- 30.9% versus basal conditions, P < 0.01) counterbalanced by an exaggerated sympathetic activity (LFnu: +33 +/- 42.4%, P < 0.05) at the sinus node. Interestingly, we could observe an enhanced cardiac baroreflex response during the period following the inhalation of the hypoxic mixture (+130.6 +/- 15.6% of basal conditions, P < 0.001). There is a relationship with a significant and abrupt increase in the parasympathetic control of HR (mean HR reached 111 +/- 8.1% of the mean basal HR, P < 0.01). These results suggest that brief exposure to hypoxia under rate-controlled ventilation is associated with a significant alteration in the spontaneous cardiac baroreflex. This important cardiac autonomic imbalance is followed by a significant increase in the cardiac parasympathetic drive even after the disappearance of the hypoxic stimulus.