Congenitally athymic nude (nu/nu) mice showed higher sensitivity to intratestical infection of Sporothrix schenckii than phenotypically normal littermates (nu/+). Active immunization with viable cells enhanced the resistance to intravenous (i.v.) infection of this fungus in BALB/c mice. Nu/nu mice transferred with immune spleen cells acquired the enhancement of resistance to the infection with S. schenckii, but not ones with normal spleen cells. Pre-treatment of OK-432 (Picibanil), one of the macrophage activating agents, enhanced resistance to i.v. infection of this fungus in BALB/c mice. On the other hand, pretreatment of carrageenan, one of the macrophage inhibitors, impaired the resistance. This fungus was intracellularly killed by peritoneal macrophage from OK-432 treated or immunized mice but not by those from normal mice in vitro. These results suggest that activated macrophage, that was mediated by T cells, play an important role in the resistance to S. schenckii in mice.