We compared the hemodynamic and blood gas data from anesthetized dogs given 0.15% carbon monoxide (CO) to breathe (INH group) and from dogs injected with 100% CO intraperitoneally while breathing room air (ITP group). The animals were observed for a period of 150 min after reaching a level of 50% carboxyhemoglobin (HbCO). The time required to reach this level was similar for both groups, i.e., 102 +/- 54 and 90 +/- 21 min for the ITP and INH groups, respectively. The average HbCO% for the duration of the experiment was 58.3 +/- 2.4 and 62.9 +/- 1.5% for the ITP and INH groups, respectively. All the animals survived in each group. There was no significant difference in their hemodynamic response to CO, except for a higher mean systemic blood pressure in the INH group. This difference was also present during the base-line measurements, suggesting that it was not related to the effects of CO. Following the 150-min comparison period, we attempted to precipitate a terminal cardiovascular crisis by increasing the amount of CO given. The animals in the ITP group lived indefinitely as the result of a “plateau” effect in the level of HbCO%. The measured HbCO% level did not rise above 70% regardless of the amount of CO injected into the peritoneal space. Those in the inhalation group died with an average HbCO% of 80.0 +/- 3.5%. It is concluded that the toxic effect of CO is the result of impaired O2 delivery to the peripheral tissues.