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 (VA/Q) 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 VA/Q mismatching, characterized by the presence of a small percentage of blood flow to low VA/Q units (VA/Q less than 0.1) (4 +/- 1%). In contrast, patients whose lungs were MV had larger shunts (22 +/- 5%) and greater percent of perfusion to low VA/Q units (11 +/- 5%). While breathing 100% O2, shunt remained unchanged but the dispersion of the pulmonary blood flow distribution (log SDQ) (normal range, 0.3-0.6) increased in each group (from 1.04 +/- 0.10 to 1.29 +/- 0.13 in SB and from 1.40 +/- 0.11 to 1.64 +/- 0.14 in MV; P less than 0.05 each), suggesting release of hypoxic pulmonary vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)