Viruses and other possible causative agents should be sought light and electron microscopically in all cases of ill-defined diseases including "sarcoid." Ideally, tissue should be prepared for electron microscopic examination as soon as a specimen is obtained; however, when this has not been done, tissue preserved in formalin solution can be used. Viruses, some bacteria, and other agents suspected on the basis of light microscopic findings can be verified electron microscopically by reprocessing paraffin-embedded tissue from areas that show smudge cells, focal necrosis with atypical cellular proliferation, and nuclear inclusions. Electron microscopically, all dying cells show swelling and rupture of cellular organelles and membranes; reactive changes include proliferation of branching tubules and paracrystalline and other types of proteinaceous precipitates (inclusions) in both the nucleus and cytoplasm. Qualitative and quantitative changes of cellular organelles, fibrils, microvilli, and intercellular junctions reflect hyperplasia, metaplasia, or dysplasia of the cell and may enable identification of the diseases, e.g., desquamative interstitial pneumonia. In various conditions, basal laminae become irregular, disruptive, or reduplicated following epithelial necrosis and regeneration. Electron microscopic evidence of immunologic damage to basal lamina and cells and immuno-electron-microscopic features of the lung in general require further studies. Electron microscopic features of transbronchial biopsy specimens may be diagnostic in cases of alveolar proteinosis, histiocytosis X, and amyloidosis. Ultrastructural abnormalities of cilia are common; primary ciliary defects are rare. Finally, light microscopic, scanning electron microscopic, and x-ray energy-dispersive spectrometric examinations of paraffin-embedded sections appear most practical for the pathologic evaluation of cases of pneumoconiosis.