To determine the histopathologic basis for computed tomographic (CT) interpretation of smokers' lung and the accuracy of CT in the detection of alterations related to cigarette smoking, parenchymal lung lesions were studied from 41 heavy smokers who underwent thoracotomy for removal of a solitary pulmonary nodule. CT scanning of the resected lungs, corresponding exactly to the sections seen on preoperative CT scans, resulted in the following pathologic-CT correlations. Areas of ground-glass attenuation seen on preoperative CT scans (n = 11 [27%]) were related to three main histologic features: (a) accumulation of pigmented macrophages and mucus in the alveolar spaces, associated with mild interstitial inflammation and/or fibrosis (n = 7); (b) thickening of the alveolar walls with inflammatory cells with normal alveolar spaces (n = 3); and (c) presence of organizing alveolitis (n = 1). Parenchymal micronodules depicted presurgically (n = 4 [10%]) corresponded to bronchiolectases with peribronchiolar fibrosis (n = 4) associated with obliterative bronchiolitis in one patient. When emphysema was detected presurgically (n = 21 [51%]), it was always present at pathologic study to a higher extent than initially suspected.