Short-term intermittent hypoxia leads to sustained sympathetic activation and a small increase in blood pressure in healthy humans. Because obstructive sleep apnea, a condition associated with intermittent hypoxia, is accompanied by elevated sympathetic activity and enhanced sympathetic chemoreflex responses to acute hypoxia, we sought to determine whether intermittent hypoxia also enhances chemoreflex activity in healthy humans. To this end we measured the responses of muscle sympathetic nerve activity (MSNA, peroneal microneurography) to arterial chemoreflex stimulation and deactivation before and following exposure to a paradigm of repetitive hypoxic apnea (20 sec per min for 30 min; O₂ saturation nadir 81.4 ± 0.9%). Compared to baseline, repetitive hypoxic apnea increased MSNA from 113 ± 11 to 159 ± 21 units/min (P = 0.001) and mean blood pressure from 92.1 ± 2.9 to 95.5 ± 2.9 mmHg (P = 0.01; n = 19). Furthermore, compared to before, following intermittent hypoxia the MSNA (units/min) responses to acute hypoxia (FiO₂ 0.1, for 5 min) were enhanced (pre vs. post: +16 ± 4 vs. +49 ± 10%; P = 0.02; n = 11) whereas the responses to hyperoxia (FiO₂ 0.5, for 5 min) were not changed significantly (P = ns; n = 8). Thus, 30-min of intermittent hypoxia is capable of increasing sympathetic activity and sensitizing the sympathetic reflex responses to hypoxia in normal humans. Enhanced sympathetic chemoreflex activity induced by intermittent hypoxia may contribute to altered neurocirculatory control and adverse cardiovascular consequences in sleep apnea.