The development of the high-resolution computed tomography (HRCT) has improved the ability to detect and quantify emphysema in various groups of patients with chronic airflow obstruction (COPD). Significant correlations have previously been found between indices of air flow obstruction, hyperinflation, reduced diffusing capacity for carbon monoxide (DL_CO), and the extent of emphysema (emph.%) assessed by HRCT. However, the relationship between emph.% and ventilation-perfusion (V_A/Q) inequality in COPD is unknown. Twenty COPD patients with a mean forced expiratory volume in 1 s (FEV₁) of 38.2 (±15.5)% in percent of predicted value (%P), a meanP aO₂ value of 9.6 (±1.3) kPa, and a mean diffusing capacity of 43.6 (±23.0)%P, were subjected to measurements by the multiple elimination inert gas technique (MIGET). The extent of emphysema was determined by HRCT at both full inspiration, emph. I (%) and at full expiration, emph. E (%), with a cut-off limit of −910 Hounsfield Units (HU) using the “Density Mask” method. The ventilation directed towards highV_A /Q areas was 7.3 (±10.2)% and the mean ventilation (V -mean) was elevated about three times compared to normal. The mean emph.(I)% and emph.(E) was 45.6 (±16.9) and 32.7 (±19.0)%, respectively. Significant correlations were shown between the emphysema extent and several lung function parameters, but no correlation was found between the emphysema extent and the V_A/Q relationships or the blood gas values. Reduced DL_CO%P correlated with less high V_A/Q ventilation (r=0.73, P<0.05) for the subgroup of COPD patients with DL_CO(%P) less than 50% (n=12). Conclusions: In COPD patients, suffering from moderate to severe emphysema without severe blood gas impairment, no correlation was shown between the extent of emphysema, as assessed by HRCT, and the severity of ventilation-perfusion inequality. A substantial collateral ventilation in severe emphysema may be a mechanism that prevents a deterioration in V_A/Q relationships and in blood gas levels.