Backgropund: Sepsis may impair O-2 extraction due to blood flow redistribution or decreased utilization of the available oxygen. Methods: We assessed the effect of endotoxemia on systemic and regional O-2 extraction and lactate handling in pigs, randomized to receive either endotoxin (0.4 mu g kg(-1) h(-1); n = 10) or saline infusion (controls; n = 9) for 12 h. Results: High baseline regional and systemic O-2 extraction in the endotoxin group (median 56%, range 45-77%) and in the controls (67%, 49-72%) was maintained until the end of the experiment (endotoxin group: 60%, 50-71%; controls: 60%, 50-74%) despite hypotension and a decrease in stroke volume in endotoxic animals. Hepatic lactate exchange decreased during endotoxemia from 14 mu mol kg(-1) min(-1) (range 10-28 mu mol kg(-1) min(-1)) to 10 (range 3-15) mu mol kg(-1) min(-1); P < 0.01), but remained stable in the controls, with 13 mu mol min(-1) (4-18 mu mol min(-1)) at baseline and 7 mu mol min(-1) (3-17 mu mol min(-1)) after 12 h of saline infusion. Conclusion: The high and sustained oxygen consumption and oxygen extraction in this endotoxemic model speak against any major impairment of hepatosplanchnic or systemic oxygen extraction and oxidative metabolism. The reduced hepatic lactate exchange despite an unchanged hepatic lactate influx suggests altered metabolic activities independent of oxygen consumption.