A large number of cases (303) of primary granulomatous inflammation, present in surgically removed specimens from a broad range of locations, were reviewed and examined in detail. The granulomas were characterized as to morphology, location, and etiology. Epithelioid granulomas without necrosis were most frequently due to sarcoidosis and mycobacterial infection, while epithelioid granulomas with necrosis were most commonly due to mycobacterial infection, fungal infection, rheumatoid arthritis and sarcoidosis. Mature granulomas, most of which did not contain necrosis, were generally due to foreign bodies. The responsible etiologic agents were generally identified in granulomas due to fungi, bacteria, or foreign bodies (92%). However, mycobacteria were infrequently identified in granulomas, even when the lesions were examined by the auramine-O technique (31%). Overall, the majority of the granulomas (76%), were due to five causes: sarcoidosis, mycobacterial infection, particulate inclusions, fungal infection, and rheumatoid arthritis. The frequency of a given etiology, however, varied widely depending on the location of the lesion. By classifying granulomas morphologically and knowing their location, useful predictive information concerning the etiology of a given granuloma, beyond that obtained by histochemical stains, could be derived.