Computed Tomography (CT) has been proved to be the most accurate imaging modality to diagnose emphysema in vivo. Our study was aimed at comparing different CT methods for pulmonary emphysema quantification in patients with severe chronic obstructive pulmonary disease (COPD). Forty-six consecutive inpatients affected with COPD underwent high resolution CT (HRCT). Three scans were acquired at 3 preselected anatomic levels at both full inspiration and expiration. Three different observers were asked to subjectively evaluate, under blind conditions, the extent alone and both the severity and the extent of emphysema on the 6 scans. HRCT findings were also analyzed quantitatively by measuring the mean CT number in Hounsfield Units (HU) and the % of lung area with CT numbers < -900 HU (pixel index). Quantitative CT data were compared with reference values obtained in 7 normal nonsmokers. The CT visual score of emphysema exhibited medium-high interobserver reproducibility with correlation coefficients ranging from 0.80 to 0.96 and a good correlation with pulmonary function tests, particularly relative to the assessment of the extent of emphysema alone as expressed by one observer. CT quantification demonstrated an excellent correlation with functional indices of expiratory airflow, lung volumes and diffusion coefficients (p < 0.001). The expiratory measurements were better than the inspiratory ones while the analysis of both CT number and pixel index gave comparable results. Only the CT expiratory quantitative data allowed to differentiate the patients affected with COPD from the controls. In conclusion, the severity of emphysema as expressed by CT correctly reflects the functional impairment of patients with severe COPD.(ABSTRACT TRUNCATED AT 250 WORDS)