Fourteen patients suffering from severe but stable chronic airway obstruction were studied while breathing room air and mildly hyperoxic mixture (26%). The data were collected at the end of each 30 min randomized breathing period. The multiple inert gas elimination technique was used to detect alterations in ventilation-perfusion (VA/Q) mismatching. Ventilatory, arterial and mixed venous blood gases, and hemodynamic measurements were made simultaneously. To show a possible effect of O2 on hypoxic pulmonary vasoconstriction (HPV), the fractional part of cardiac output perfusing low VA/Q areas was separated using as upper limit of VA/Q the compartments with PAO2 70, 60 and 50 mmHg while breathing oxygen, compared to the percentage of blood flow in the same areas limited by the same VA/Q unit in air breathing conditions. Only a few changes due to O2 are statistically significant: 1) a rise in PaO2 (+20.2 +/- 8.3 mmHg) and PvO2 (+4.2 +/- 2.18 mmHg) without any change in ventilation, respiratory frequency, pH, PaCO2, haemodynamics and overall criterion of distribution; 2) a moderate increase in inert gas dead space; 3) an increase in the percentage of blood flow under the limit when chosen at 50 mmHg (+3 +/- 2.8%). This change could be related to an inhibition of HPV response while breathing O2 in compartments previously placed above the limit in air. Consequently, their VA/Q decrease and their perfusions are summed with those under the limit in O2. These data suggest that mild hyperoxia has a slight but real deleterious effect on pulmonary gas exchange.