An in vitro generated BV-2 microglial cell line has been transferred intracerebrally into syngeneic immunocompetent mice prior to local challenge with Candida albicans. The transfer resulted in the establishment of local protection against a lethal dose of C. albicans, which was accompanied by an impairment of yeast growth in the brain and kidneys. Upon histological examination of brain sections from BV-2 cell-pretreated mice, it was found that the size and number of granulomas was reduced as compared to untreated controls receiving Candida alone. These observations provide direct evidence that microglia play a crucial role in the local defense against intracerebral infections.