Peripheral respiratory chemoreceptors monitor breath-by-breath changes in arterial CO2 and O2, mediating ventilatory changes through a peripheral chemoreflex. Intermittent bouts of hypoxia (IHx) elicit hypoxic ventilatory responses, with well-described experience-dependent effects (EDEs), mostly from work in animal models using 5-min intermittent bouts. These EDEs include post-hypoxia frequency decline (PHxFD), progressive augmentation (PA), and long-term facilitation (LTF). Comparisons of these EDEs between animal models and humans using similar IHx protocols have not been extensively performed. In addition, whether shorter bouts of IHx elicit EDEs in humans is unknown. Respiratory (frequency, inspiratory tidal volume and minute ventilation; fR, VTI and V̇I) and cardiovascular (heart rate and mean arterial pressure; HR and MAP) variables were measured during and following two patterns of acute isocapnic IHx in 14 healthy human participants: 5×5-min on/off and 5×90-sec on/off (normoxia vs. hypoxia [45 Torr PETO2]) using steady-state dynamic end-tidal forcing. We found that (a) PHxFD and PA were not present in either pattern of IHx (P>0.14), but that (b) LTF was present in V̇I following 5-min on/off IHx (P<0.001) and 90-sec on/off IHx (P<0.001) and (c) LTF was present in MAP following 5-min on/off IHx (P<0.001) but not following 90-sec on/off IHx (P=0.058). Our data suggest that (a) most EDEs characterized in animal models in response to acute IHx are absent in healthy humans and/or absent following shorter IHx bouts and (b) caution should be exercised when using reduced animal models to extrapolate understanding of human responses to blood gas perturbations.