Previous studies on autopsy specimens or surgically resected lobes or lungs have reached varying conclusions regarding the importance of small airways disease and emphysema in causing fixed expiratory airflow limitation in patients with chronic obstructive pulmonary disease (COPD). We obtained high resolution CT scans of the lung and lung function in 56 consecutive patients with fixed expiratory airflow limitation. There was poor correlation between CT emphysema score and either FEV1/FVC% (r = -0.36) or FEV1 % predicted (r = -0.20). In only 10 of the 35 patients with FEV1 < 50% predicted, the CT emphysema score was > 40, indicating significant emphysema. A strong negative correlation between diffusing capacity % predicted and diffusing capacity per alveolar volume and CT emphysema score was found only in patients with FEV1 > or = 1 L (r = -0.75, p < 0.0001). Thus, emphysema does not appear to be primarily responsible for expiratory airflow limitation in COPD. A low diffusing capacity may be spuriously misleading in patients with FEV1 < 1 L and no or trivial emphysema.