In the present study, in order to clarify the defense mechanisms against S. schenckii infections, we examined the tissue reactions of mice against the pathogen over a period of time by both light and electron microscopy. The histological features were, at an early stage, a mixed cell granuloma consisting of polymorphonuclear leukocytes (PMNs) and macrophages, and, later on, enlargement and vacuolation of the macrophages at the periphery. In electron microscopy, blastospores had been phagocytized by the PMNs and macrophages, and no extracellular blastospores were seen. PMNs taking up blastospores were phagocytized by other PMNs or by macrophages. After 3 or 4 months, the phagosomes of the macrophages had grown in size, and contained a number of blastospores. During the experiment, the ultrastructure of the blastospores was well preserved, and their viability was considered high. Of the defense mechanisms against S. schenckii infection, PMN phagocytosis is of great importance, but the fact that proliferation of this organism was observed within the macrophages, suggested that the macrophages were not able to destroy the organisms, but rather were responsible for the disease becoming chronic.