The authors reviewed 46 cases of idiopathic pulmonary fibrosis with usual interstitial pneumonia (UIP), correlating findings on high-resolution computed tomographic (HRCT) scans with findings in specimens obtained at open lung biopsy and autopsy. The following HRCT findings were observed: (a) an accumulation of small cystic spaces with thick walls, (b) air bronchiolograms within areas of intense lung attenuation, (c) rugged pleural surfaces, (d) irregularly thickened pulmonary vessels, (e) bronchial wall thickening, and (f) slightly increased lung attenuation. Macroscopic honeycombing correlating with small cystic spaces was demonstrated at HRCT and pathologic examination. Air bronchiolograms in the areas of intense lung attenuation (ie, microscopic honeycombing) corresponded to dilated bronchioles (greater than 1 mm in diameter) with fibrosis. Irregularly thickened vessels and bronchial walls and irregular pleural surfaces were the result of fibrosis in the periphery of the secondary pulmonary lobules. Areas of slightly increased lung attenuation seen on the HRCT scans correlated with patchy alveolar septal fibrosis or inflammation. The authors conclude that microscopic honeycombing and a perilobular distribution in UIP may be clearly identified with HRCT.