The mechanisms of abnormal gas exchange in patients with pneumonia and the gas exchange response while breathing high inspired O2 concentrations have not been clearly elucidated. To this end, we studied 23 inpatients with pneumonia and mild to severe arterial hypoxemia and/or increased alveolar – arterial O2 difference. Ventilation-perfusion (JOURNAL/anet/04.02/00000542-199111000-00009/ENTITY_OV0312/v/2017-07-22T060031Z/r/image-pngA/JOURNAL/anet/04.02/00000542-199111000-00009/ENTITY_OV0422/v/2017-07-22T060031Z/r/image-png) distributions were obtained upon breathing room air (or maintenance inspired oxygen fraction) and 100% O2 in random order. Subjects were divided in two groups according to whether they were spontaneously breathing (SB, n = 13) or their lungs were mechanically ventilated (MV) because of acute severe respiratory failure (n = 10). The SB patients showed only small amounts of shunt (7 ± 2%) (mean ± standard error) and moderate JOURNAL/anet/04.02/00000542-199111000-00009/ENTITY_OV0312/v/2017-07-22T060031Z/r/image-pngA/JOURNAL/anet/04.02/00000542-199111000-00009/ENTITY_OV0422/v/2017-07-22T060031Z/r/image-png mismatching, characterized by the presence of a small percentage of blood flow to low JOURNAL/anet/04.02/00000542-199111000-00009/ENTITY_OV0312/v/2017-07-22T060031Z/r/image-pngA/JOURNAL/anet/04.02/00000542-199111000-00009/ENTITY_OV0422/v/2017-07-22T060031Z/r/image-png units (JOURNAL/anet/04.02/00000542-199111000-00009/ENTITY_OV0312/v/2017-07-22T060031Z/r/image-pngA/JOURNAL/anet/04.02/00000542-199111000-00009/ENTITY_OV0422/v/2017-07-22T060031Z/r/image-png