Destruction of alveolar walls is considered by most observers to be the most important part in the definition of emphysema, yet it has never been precisely defined and quantitated. We therefore attempted to devise a reliable microscopic technique to quantitate alveolar destruction that would be both sensitive to disease and easy to perform. Using a point-count system, we obtained an index of parenchymal destruction that represents the percentage of destroyed space as a fraction of the total alveolar and duct space. We have called this measurement the destructive index (DI). In the lungs of 8 nonsmokers and 23 smokers, we quantitated the DI and compared it with the mean linear intercept (Lm) and with pulmonary function in smokers. Although Lm was not significantly different in the 2 groups, significant differences between the DI of smokers and nonsmokers (p less than 0.005) were found. In addition, the DI correlated with FEV1(-0.43, p less than 0.05), MMEF (r = -0.44, p less than 0.05), and recoil pressure at 90% TLC (r = -0.61, p less than 0.05) in smokers. These findings suggest that the destructive component of emphysema can be easily quantitated microscopically, occurs in smokers before dimensional changes are evident (i.e., increased Lm), and influences lung function. Therefore, the quantitation of this destruction (DI) could add greatly to the microscopic definition of emphysema, complementing the information given by the dimensional component of emphysema (Lm).