Arterial oxygenation was measured in patients being ventilated artificially for respiratory failure, initially at the FIO2 that had been selected clinically to achieve PaO2 at least normal, and then at each of two or three progressively increased FIO2 values up to about 0.9. Impairment of oxygen transfer was assessed by the difference between calculated pulmonary end-capillary and arterial oxygen content (Cc'O2-CaO2). Reasons are presented to support the assumption that this value indicates the degree of venous admixture. In patients with severely impaired gas exchange ((Cc'O2-CaO2) greater than 1 ml dl-1), the first increase in inspired oxygen decreased the impairment: less severely impaired lungs showed no change. The observations are consistent with the ventilation/perfusion mismatch hypothesis and do not show that increased oxygen impairs pulmonary oxygenating efficiency.