A variety of silicotic lesions derived from thoracic silicosis via lymphohematogenous spread to the liver, spleen, bone marrow, and extrathoracic lymph nodes are described. The morphologic features of these lesions depend on the extent of macrophage aggregation, the occurrence of fibrogenesis, and the development of necrosis and degradative changes in macrophages and adjacent extracellular matrix, presumably caused by lysosomal enzymes released from macrophages. Ultrastructurally, the degenerative alterations of matrix material include longitudinal splitting and breakage of collagen fibrils into segments one and three quarters the length of the original fibrils and deposition of flocculent electron-dense material either focally or diffusely around collagen fibrils. The corresponding changes viewed light microscopically are those of fibrinoid necrosis. The sclerohyaline nodule, the characteristic lesion of silicosis, includes all of these features as it evolves through nodular histiocytic and subsequent fibrohistiocytic phases. Its ultimate morphology appears to be determined by the reassembly of the degraded matrix into non-native, fibrous long-spacing collagen via a spiny collagen intermediary. The sclerohyaline nodule occurs infrequently in the spleen and liver, although less typical lesions caused by silica alone or admixed with other dusts seem to occur more commonly in these organs. These lesions appeared as loose or nodular histiocytic or fibrohistiocytic aggregates. Nonspecific fibrous nodules or more extensive fibrosis, as seen in portal triads, may represent advanced stages of such lesions. Acute or healed focal segmental glomerulonephritis occurred in 40 per cent of the cases, suggesting that it may be an important remote effect of silicosis. Continuous destruction of lymphocytes adjacent to silicotic nodules may be an antigenic source of the high concentration of autoimmune reactants described in silicosis.