Time-course changes of injected amyloid fibrils into non-treated and amyloid-laden mice were studied using the technique of ultrastructural histochemistry and immunoelectron microscopy. Light microscopically, a granuloma was formed in the subcutaneous tissue in both group 3 days after the injection of extracted amyloid fobrils. An accumulation of a large number of microphages, of which cytoplasm conrained several vacuoles and phagocytosed amyloidfibrils, was seen in the granuloma. The Congo red staining became weaker with advance of time after the phagocytosis of the injected amyloid fibrils. Ultrastructurally, a large number of phagosomes and phagolysosomes (acid phosphatase positive) were detected in the cytoplasm of the macrophages throughout the present study. At the early stage, in most of the macrophages, oval to rhomboid-shaped phagpspmes contained clearly recognizable amyloid fibrils, but, at the late stage, phagosomes became smaller and more round in shape without any fibrillar structures in them. However, in the latter phagosomes, several gold particales were still labeled by immunoelectron technique using anti-murine AA antiserum. These findings were similar in both non-treated and amyloid-laden mice when compared with them at the same period after the injection of amyloid fibrils. From the present, it is suggested that the role of the macrophages exists until the formation of amyloid fibrils.