The fungus Cryptococcus neoformans is an important opportunistic pathogen for patients with AIDS. C. neoformans infections frequently involve the brain and are often fatal. In the setting of AIDS C. neoformans infections are incurable and new treatment strategies are urgently needed. Passive administration of antibody is a potential therapeutic option for the prevention and treatment of C. neoformans. The IgG1 murine monoclonal antibody 2H1 to the capsular polysaccharide of C. neoformans was studied for its ability to modify the course of lethal intracerebral cryptococcal infection in mice. Intraperitoneal administration of antibody 2H1 resulted in small, yet significant, prolongations in the average survival of mice given intracerebral infection and reduced the number of C. neoformans colonies in brain tissue. Histopathological examination of brain tissues revealed a diffuse cryptococcal meningitis with fewer organisms in the brains of mice that received antibody 2H1 than in the control group. Thus, systemic administration of a monoclonal antibody can modify the course of lethal intracerebral C. neoformans infection in mice by prolonging survival and decreasing fungal burden in brain tissues.