The causes of arterial hypoxemia, which is often associated with head injury, were investigated in 12 studies performed on 11 unconscious, tracheotomized, spontaneously breathing patients with head injury and no gross pathologic changes in the lungs. After inhalation of a gas mixture containing 0.09 per cent carbon monoxide, 19.41 per cent oxygen, and 80.5 per cent nitrogen and another mixture containing 0.07 per cent carbon monoxide in oxygen, ventilation, and arterial, mixed venous, end-tidal, and mixed expired gases were measured. While breathing air, patients with head injuries had normal alveolar oxygen tension (mean ± SE: 107 ± 1.8 mm Hg) with severe arterial hypoxemia (57 ± 2.6 mm Hg) and thus an abnormally high alveolar-arterial oxygen difference (50 ± 3.0 mm Hg). During oxygen breathing, the alveolar-arterial oxygen difference was 246 ± 20.1 mm Hg. Pulmonary diffusing capacity for carbon monoxide was diminished to 19.31 ml per min per mm Hg (predicted: 28.19 ml per min per mm Hg). Venous admixtur...