Following systemic inflammation, the lung induces an isoenzyme of heme oxygenase (HO-1), catalyzing carbon monoxide (CO) production through breakdown of heme molecules. However. it is still debated why the paradoxical arterio-venous carboxyhemoglobin (COHb) difference occurs only during critical illness but not in healthy volunteers. To elucidate whether oxygen fractions at (sub-)physiologic ranges alter the affinity of CO to hemoglobin (Hb), we performed an in vitro laboratory experiment. in which we exposed venous blood samples to fixed CO-doses at incrementing oxygen fractions (FiO(2)). ANOVA demonstrated that the affinity of CO (200 and 400 ppm) to Hb progressively increased with an FiO(2) from 0% to 15%, whereas at higher oxygen tensions this effect vanished. This might explain why the arterio-venous COHb difference found in critically ill patients is not reproducible in healthy adults, since the latter ones are characterized by higher venous oxygen saturations. (C) 2002 Elsevier Science (USA). All rights reserved.