Since the original description of desquamative interstitial pneumonitis in 1967, several investigators have questioned the specificity of the disease. The concept of desquamative interstitial pneumonitis and usual fibrosing interstitial pneumonitis as two manifestations of a nonspecific disease spectrum has been proposed. Twenty-six patients with desquamative interstitial pneumonitis were evaluated with respect to clinicopathologic correlates. Biopsies were reviewed without knowledge of the patients' clinical course. The absolute histopathologic criteria for the diagnosis were (1) intra-alveolar accumulations of free alveolar cells with PAS-positive diastaseresistant cytoplasmic granules; (2) mononuclear cell interstitial inflammation; and (3) absence of necrosis, hyaline membranes, intra-alveolar fibrosis, asbestos bodies, and birefringent crystalline dust material. Transmission electron microscopic studies revealed the dominant alveolar lining cell to be the granular pneumocyte, with a prominent population of free alveolar macrophages. Patients were segregated into group 1 (cellular phase) and 2 (cicatrized phase). Although favorable short-term responses to corticosteroid therapy were observed in both groups, long-term responses were variable. Apparent complete remissions were noted in both groups.