The diagnostic value of chest radiography and high-resolution computed tomography (CT) in chronic diffuse interstitial lung disease (CDILD) was assessed in 140 consecutive patients with diffuse infiltration of the lung visible at radiography. Radiographs and CT scans were separately read by three independent observers without knowledge of clinical and pathologic data. The observers listed the three most likely diagnoses and recorded the degree of confidence they had in their choice on a 0%-100% probability scale. Findings at radiography and high-resolution CT were recorded by each observer and were used for a stepwise discriminant analysis between diagnoses. First-choice diagnoses of all three observers that were made with a high level of confidence (probability, greater than or equal to 75%) were more accurate with CT than with radiography (P less than .001). The superiority of high-resolution CT over radiography was most obvious for histiocytosis X and sarcoidosis; in cases of pulmonary fibrosis, CT was not significantly different from radiography. The interobserver agreement for the proposed diagnosis was significantly better with high-resolution CT (P less than .001). Twenty-one of 26 radiographic findings and 21 of 25 CT findings were discriminant. Stepwise discriminant analysis revealed the superiority of CT over radiography, since the ranking of all findings showed that the four most discriminant findings, and eight of the first 12 findings, were revealed with CT.