It is still unclear whether the paradoxical arteriovenous carboxyhemoglobin (COHb) difference found in critical illness is due to increased COHb production by the lung, or whether this gradient is caused by technical artifacts using spectrophotometry. In healthy and matched endotoxemic sheep, blood gases were analyzed with a standard ABL 625 and the updated version, an ABL 725. The latter one was accurately calibrated for COHb wavelengths (SAT 100) to eliminate the,FCOHb dependency on oxygen tension. All endotoxemic sheep exhibited a hypotensive-hyperdynamic circulation and a pulmonary hypertension. Interestingly, arteriovenous COHb difference occurred in both healthy and endotoxemic sheep (P < 0.001 each). Arterial and central venous COHb concentrations determined with the ABL 625 were significantly lower than those measured with the ABL 725 (P < 0.001 each). We conclude that (a) arteriovenous COHb difference per se does not reflect critical illness and (b) measurements with an ABL 625 underestimate COHb concentrations. (C) 2002 Elsevier Science (USA). All rights reserved.