This study was aimed at clarifying the effect of carbon dioxide (CO2) on the toxicity of carbon monoxide (CO) in the hypoxic condition. In order to evaluate the coexistent toxicity of CO2 and CO under hypoxic hypoxia, we investigated the difference of CO toxicity between under the hypoxic and hypercapnic hypoxia in point of lethality in conscious male mice. Furthermore, we measured blood gases (pO2 and pCO2), pH, COHb concentration, and blood pressure (BP) and heart rate (HR) in urethane anesthetized male rabbits inhaled with 2 toxic gases: N2-toxic gas (O2 5.0%, CO 1.8%, N2 93.2%) and CO2-toxic gas (O2 5.0%, CO2 16.0%, CO 1.8%, N2 77.2%). The animals were inhaled with the 2 toxic gases until the BP reached 0 or 20 mmHg. In the latter case, when the BP reached 20 mmHg, the animals were inhaled with air and were intravenously infused with saline (20 ml/kg/30 min). Conscious mouse experiment: In the both types of hypoxia, LC50 were decreased with the decrease of O2 concentration and the LC50 of CO in hypercapnic hypoxia was significantly lower than that in nitrogen-replacement hypoxia in the range of 12% and 9% of O2 concentration in male mice. BP 0 mmHg-group experiment in rabbits: All the rabbits inhaled with N2-toxic gas or CO2-toxic gas died. The time to BP 0 mmHg in CO2-toxic gas group (7.8 +/- 0.33 min) was shorter than that in N2-toxic gas group (11.5 +/- 1.00 min). Although both toxic gases lowered pO2 level and elevated COHb% of the blood, CO2-toxic gas extremely elevated pCO2 level by 80-100 mmHg corresponding to lowering the serum pH by 0.37-0.45. BP was firstly elevated during 2-3 minutes by inhalation of these toxic gases and was finally lowered to die. HR decreased continuously after the inhalation of toxic gases until the animals died. BP 20 mmHg-group experiment in rabbits:Recoveries of COHb%, pCO2 level and pH of the blood in N2-toxic gas intoxication were significantly faster than those in CO2-toxic gas group. The times to COHb 10% were 64.2 min and 78.2 min in N2-toxic gas and CO2-toxic gas, respectively. But, there was no significant difference between N2-toxic gas and CO2-toxic gas intoxications in the recoveries of pO2 level, BP and HR. The above results suggest that CO2 potentiates the CO-intoxication under hypoxic hypoxia and our methods of coexistent gas toxicity may be useful for examining the gas toxicity in fire accident.