To understand the factors influencing breath-holding performance, we tested whether the hypoxic (HVR) and hypercapnic ventilatory responses (HCVR) were predictors of the extent of maximal breath-holds as measured by breath-hold duration, the lowest oxyhemoglobin saturation (SpO2min), lowest calculated PaO2 (PaO2min) and highest end-tidal PCO2 (PETCO2max) reached. Steady state isocapnic HVR and hyperoxic HCVR were measured in 17 human volunteers. Breath-holds were made at total lung capacity (TLC), at TLC following hyperventilation, at functional residual capacity, and at TLC with FIO2 = 0.15. SpO2 was measured continuously by pulse oximetry, and alveolar gas was measured at the end of breath-holds by mass spectrometry. PaO2min was calculated from SpO2min and PETCO2max. HVR was a significant predictor of both SpO2min and PaO2min. HVR and forced vital capacity were predictors of breath-hold duration by multiple linear regression. HCVR had no significant predictive value. We conclude that HVR, but not HCVR, is a significant predictor of breath-holding performance.