The growing urge to breathe that occurs during breath-holding results in development of involuntary breathing movements (IBMs). The present study determined whether IBMs are initiated at critical levels of hypercapnia and/or hypoxia during maximal apnoea. Arterial blood gasses at the onset of IBM were monitored during maximal voluntary breath-holds. Eleven healthy men performed breath holds after breathing air, hyperoxic-normocapnia, hypoxic-normocapnia, and normoxic-hypercapnia. Pre-breathing of the gas mixtures facilitated the IBM onset, reducing the time-to-onset for ~46% (hyperoxic condition) and for ~80% (hypoxic condition) compared to the normoxic air breathing time. A strong correlation (R = 0.83, P = 0.002) between arterial partial pressure of CO2 (PaCO2PaCO2) at IBM onset after pre-breathing hyperoxic and hypercapnic gas mixtures was observed, suggesting the existence of a possible IBM PaCO2PaCO2 threshold level of ~6.5 ᠰ.5 kPa. No clear "threshold" was observed for partial pressure of arterial O2 (PaO2PaO2). However, we observed that IBM onset was influenced, in part, by an interaction between PaO2PaO2 and PaCO2PaCO2 levels during maximal apnoea. This study demonstrated the complex interaction between arterial blood-gases and the physiological response to maximal breath holding.