We compared the accuracies of high-resolution CT (HRCT) and conventional CT in determining the specific diagnoses in 75 consecutive patients with chronic diffuse infiltrative lung disease. Without knowledge of clinical or pathologic data, two reviewers independently assessed three separate sets of CT scans in random order: three HRCT scans, three 10-mm collimation CT scans obtained at the same levels as the HRCT scans, and a complete conventional CT scan. The HRCT scans were obtained at the level of the aortic arch, tracheal carina, and 1 cm above the right hemidiaphragm by using 1.5-mm collimation and a high spatial resolution algorithm. Observers gave the most likely diagnosis along with their degree of diagnostic confidence. The correct diagnosis, irrespective of confidence level, was reached with 71% of the HRCT scans and with 72% of both the corresponding 10-mm and complete conventional CT scans. Confidence level 1 (definite) was reached with 49% of HRCT scans, 31% of corresponding 10-mm scans, and 43% of complete conventional CT examinations; the correct diagnosis was made in 92%, 96%, and 94% of those examinations, respectively. In none of the patients were findings on the limited HRCT scan normal when findings on the conventional CT scan were abnormal. We conclude that in most patients with chronic infiltrative lung disease a specific diagnosis can be made by obtaining a limited number of HRCT scans.