We tested the hypothesis that the decline in muscle sympathetic activity during and after 8-hours of poikilocapnic hypoxia was associated with a greater sympathetic baroreflex-mediated responsiveness. In 10 healthy men and women (n=2) we measured beat-to-beat blood pressure (Portapres®), carotid artery distension (ultrasonography), heart period, and muscle sympathetic nerve activity (microneurography), during two baroreflex perturbations using the Modified Oxford technique before, during and after 8-hours of hypoxia (84% arterial oxygen saturation). The integrated baroreflex response (SNA DBP-1), mechanical (diastolic diameter DBP-1) and neural (SNA diastolic diameter-1) components were estimated at each time point. Sympathetic baroreflex responsiveness declined throughout the hypoxic exposure and further declined upon return to normoxia (pre Hx: -8.3±1.2; 1-hour Hx: -7.2±1.0*; 7-hour Hx: -4.9±1.0*; Post Hx: -4.1±0.9* AIU min^-1 µmHg^-1 *p<0.05 vs previous time point). This blunting of baroreflex-mediated efferent outflow was not due to a change in the mechanical transduction of arterial pressure into barosensory stretch. Rather, the neural component declined in a similar pattern to that of the integrated reflex response (pre Hx: -2.70±0.53; 1-hour Hx: -2.59±0.53; 7-hour Hx: -1.60±0.34*; Post Hx: -1.34±0.27* AIU min-1 µm^-1 *p<0.05 vs pre Hx). Thus, it does not appear as if enhanced baroreflex function is primarily responsibly for the reduced muscle sympathetic nerve activity observed during intermediate duration hypoxia. However, the central transduction of baroreceptor afferent neural activity into efferent neural activity appears to be reduced during the initial stages of peripheral chemoreceptor acclimatization.