Central nervous system (CNS) oxygen toxicity, as manifested by the first electrical discharge (FED) in the electroencephalogram, can occur as convulsions and loss of consciousness. CO₂ potentiates this risk by vasodilation and pH reduction. We suggest that CO₂ can produce CNS oxygen toxicity at a PO₂ that does not on its own ultimately cause FED. We searched for the CO₂ threshold that will result in the appearance of FED at a PO₂ between 507 and 253 kPa. Rats were exposed to a PO₂ and an inspired PCO₂ in 1-kPa steps to define the threshold for FED. The results confirmed our assumption that each rat has its own PCO₂ threshold, any PCO₂ above which will cause FED but below which no FED will occur. As PO₂ decreased from 507 to 456, 405, and 355 kPa, the percentage of rats that exhibited FED without the addition of CO₂ (F₀) dropped from 91 to 62, to 8 and 0%, respectively. The percentage of rats (F) having FED as a function of PCO₂ was sigmoid in shape and displaced toward high PCO₂ with the reduction in PO₂. The following formula is suggested to express risk as a function of PCO₂ and PO₂


where P₅₀ is the PCO₂ for the half response and N is power. A small increase in PCO₂ at a PO₂ that does not cause CNS oxygen toxicity may shift an entire population into the risk zone. Closed-circuit divers who are CO₂ retainers or divers who have elevated inspired CO₂ are at increased risk of CNS oxygen toxicity.