Eight cases of acute interstitial pneumonia were studied to define the clinical and pathologic features and to determine the relationship to chronic interstitial pneumonia. Clinically, this disease differs from the chronic interstitial pneumonias by a sudden onset and a rapid course. Five patients died of respiratory failure after 23 days to 2 months, and two died of other complications after 3 1/2-6 months. An etiologic agent could not be identified in any case. The histologic hallmark was interstitial fibrosis and edema associated with type II pneumocyte hyperplasia. The fibrosis differed from that seen in the chronic interstitial pneumonias by extensive fibroblast proliferation and relatively little collagen deposition. Autoradiographic studies of tritiated thymidine (3H-TdR) uptake showed high labeling indices in interstitial cells and type II pneumocytes. Evidence of acute lung injury, including both endothelial and epithelial cell damage, was a prominent ultrastructural feature. These findings emphasize that acute interstitial pneumonia is a clinically and pathologically distinct form of interstitial pneumonia that should be separated from the group of chronic interstitial pneumonias.