Defense mechanisms of mice against Exophiala dermatitidis MM-7 were studied using congenitally athymic nude (nu/nu) mice and their heterozygous (nu/+) littermates of BALB/ c background. Each mouse was inoculated intravenously with 106 yeast cells of the fungus and sacrificed at adequate intervals by the 62nd day. Viable cells were counted from the brains, kidneys and livers of the nu/+ and nu/nu mice. Furthermore, various internal organs were examined histopathologically. The most favourite target organ of the MM-7 was the brain in both the nu/+ and nu/nu mice, followed by the kidney and liver, in that order. The susceptibility of the nu/nu mice to the MM-7 was higher than that of the nu/+ mice. Colony forming unit of 100 mg of the brain of the nu/+ mice reached a peak on the 4th day, thereafter decreased gradually and from day 40 on viable cells were never recovered. In the nu/nu mice it reached 1.1 × 104 on the 4th day. Even though the number of colony forming unit fluctuated somewhat, it was maintained until the 25th day and thereafter increased again gradually. Chief histopathological features at an early stage of the infection were both micro-abscess and micro-granuloma. These micro-granulomata were not only formed in the nu/nu mice, but also in the nu/+ mice within 2 days. From day 8 on, even in the nu/nu mice, almost all of the lesions became granulomatous. Even though the micro-granulomata in the brain of the nu/+ mice disappeared from day 40 on, considerable numbers of the lesions were observed in the nu/nu mice until the end of the experiment. It seems that the functions of T-lymphocytes are necessary for the killing of the MM-7 in the brain of mouse. The granuloma formed in the nu/nu mice was morphologically indistinguishable from that formed in the nu/+ mice. However, mononuclear cells forming the granuloma in the brain of the nu/nu mice did not kill the yeast cells which they engulfed, but suppressed multiplication of the yeast cells. Acid mucopolysaccharide was stained around these yeast cells with alcian blue. The polysaccharide might play a role as a buffered zone between the yeast cells and mononuclear cells.