We established a murine model of toxoplasmic encephalitis by using intracerebral inoculation with Toxoplasma gondii tachyzoites. Normal mice survived, but immunosuppressed mice died from progressive disease. In normal mice, necrosis developed at the site of inoculation, surrounded by areas with intense mononuclear inflammation and cyst formation; tachyzoites were not detectable after two weeks. Immunosuppressed mice had even-larger areas of tissue destruction, and tachyzoites were always detectable. Brains from cortisone-treated mice had numerous tachyzoites, but scant inflammation. Brains from cyclophosphamide-treated mice revealed cysts and a variable degree of inflammation. Compared with brains from controls, brains from cyclosporine-treated mice revealed attenuated inflammation; however, there were fewer tachyzoites and less tissue destruction than in the brains from cortisone-treated mice. The spectrum of histological findings observed in the model is similar to that observed in brains from humans with toxoplasmic encephalitis.