The purpose of this study was to evaluate the role of high-resolution computed tomography (HRCT) in the clinical diagnosis of diffuse infiltrative lung disease (DILD). Diagnostic accuracy was compared using both chest radiography and HRCT. One hundred thirty-four cases of DILD, representing 21 different diseases, were selected for study, and the disease state was confirmed either histologically or microbiologically. The HRCT images and chest radiographs, available in all cases, were reviewed separately and in random order by 20 physicians who were provided only with information on each patient's age and sex. Overall, a correct first-choice diagnosis was made in 38 percent using radiographs and in 46 percent using HRCT images (p < 0.01). The correct diagnosis was among the top three choices in 49 percent when chest radiographs were used, and in 59 percent when HRCT images were viewed (p < 0.01). The correct first-choice diagnosis increased remarkably when the HRCT was used in usual interstitial pneumonia, sarcoidosis, alveolar proteinosis, bronchiolitis obliterans organizing pneumonia, hypersensitivity pneumonitis, and pulmonary lymphangiomyomatosis. High-resolution computed tomography was confirmed to be superior to conventional radiography in the accurate diagnosis of DILD in clinical practice.