To correlate areas of parenchymal opacification on thin-section computed tomographic (CT) scans with histologic findings in patients with chronic infiltrative lung disease, the CT and histologic findings were evaluated in 29 patients with 11 such diseases. Open-lung biopsy was performed after CT. The area of predominant involvement was classified as air space, interstitium, or a mixture of both. A pathologic score of disease activity was assigned, and the extent of fibrosis was assessed whenever fibrosis was present. Parenchymal opacification on CT scans corresponded to abnormalities that affected mainly the air spaces in three patients (10%), the interstitium in 13 patients (45%), or both to a similar degree in 13 patients (45%). In 25 of 29 patients (86%), parenchymal opacification was associated with potentially treatable or reversible disease. Abnormalities considered irreversible were seen in three patients with end-stage fibrosis and one patient with talcosis. Parenchymal opacification on thin-section CT scans is a nonspecific finding in diseases that affect the air spaces, interstitium, or both but usually indicates potentially treatable or reversible disease.