The control of voluntary breath-holding is multifactorial, with contributions from cognitive factors, sex hormones, initial lung volume, lung stretch and stimulation of respiratory chemoreceptors. Breath-holding elicits chemoreceptor stimulation through increases in CO2 and decreases in O2, which change in proportion to metabolic rate. The peripheral respiratory chemoreceptors (PCRs) detect decreases in O2 (hypoxia), eliciting an increase in drive to breathe (i.e., hypoxic ventilatory response; HVR). We know that breath-hold duration is positively related to prevailing inspired oxygen. However, how HVR magnitude influences breath-hold duration (BHD) is unclear. We hypothesized that (a) voluntary BHD would be positively correlated to the initial oxygen status prior to breath-holding and (b) the HVR magnitude would be negatively correlated with voluntary BHD, within-individuals. In 16 healthy participants (25±8 yrs; BMI 24.2±3.5 kg/m2; six males), three voluntary breath-holds were performed: (a) following five breaths of 100% O2 (hyperoxia), (b) following breathing room air (normoxia), and (c) after >30 min of breathing steady-state fraction of inspired (Fi)O2 of 13.5-14% (hypoxia). In a subset of participants (n=12) we performed a transient test of the HVR, comprised of five trials of three consecutive breaths of 100% N2, where the change in ventilation was indexed against change in calculated oxygen saturation (Severinghaus transform; ΔL/min/Δ%ScO2). Subsequent analysis indicated that BHD was positively related to initial oxygen status: 89.9±9.5 sec in hyperoxia, 53.8±4.1 sec in normoxia and 40.4±3.5 sec in hypoxia (P<0.001). Interestingly, hyperoxia increased BHD by 65.1±10.9% compared to normoxia, but only reduced it by 24.5±3.6% in hypoxia compared to normoxia, and almost three-fold difference in the influence of background oxygen status. However, the HVR magnitude (0.38±0.04 L/min/-%ScO2) was not correlated with BHD in hyperoxia (r=0.46, P=0.13), normoxia (r=0.537, P=0.07) or hypoxia (r=0.45, P=0.14). Our data suggest that (a) although PCRs are likely activated during breath-holding, they contribute differentially to BHD, within-individual, (b) the magnitude of the normoxic HVR does not predict BHD, and (c) other physiological and psychological factors are more important in determining BHD.