Endogenous carbon monoxide (CO) is produced in the degradation of heme by heme oxygenase. Studies have shown that hypoxia induces heme oxygenase production of CO in vascular tissue. Because elevated plasma lactate levels are associated with tissue hypoxia, we determined if there was any correlation between lactate and carboxyhemoglobin (COHb) levels in a group of critically ill patients with a high likelihood of hypoxia. In a 7.5-month period, 5322 simultaneous arterial COHb and lactate measurements were performed routinely on 183 patients with a blood gas analyzer in the Department of Veterans Affairs Medical Center, Bronx, New York, Surgical Intensive Care Unit. Sixty-one percent of the patients had elevated lactate levels (>2.5mmol/L), and 46% had elevated COHb levels (>1.5%). Lactate levels ranged from 0.12 to 22.7 mmol/L and COHb levels from 0% to 4.8%. There was no correlation between lactate and COHb levels (r= .07 withP< .0001). Levels of endogenous CO do not increase in situations in which lactate production is increased. It is possible that changes in endogenous production of CO may not significantly affect the circulating level of COHb. Although readily available, COHb levels do not seem to be clinically useful as markers of critical illness.