Many authors have indicated that high FIO2(0.75–1.0) ventilation may increase pulmonary venous admixture. Reabsorption atelectasis is supposedly responsible for this adverse effect. The authors attempted to determine if increasing PEEP during high FIO2ventilation could eliminate the detrimental influence of the latter. In 17 patients in respiratory failure, hemodynamic and respiratory variables were measured during ventilation with FIO20.50, 0.75, and 1.0 and PEEP varying from −3 to +5 cm H2O from baseline.Before exposure to FIO2> 0.75, addition of PEEP resulted in a decrease of Qs/Qt from a mean of 26.6–21.9%. After exposure to FIO20.75–1.0, Qs/Qt remained at levels not different from baseline, even when PEEP 8 cm H2O above baseline was added.The authors conclude that ventilation with high FIO2is not useful in determining Qs/Qt, and may prevent the improvement in pulmonary venous admixture associated with PEEP therapy.