Human cerebral malaria (HCM) is a severe, often lethal, neurological complication caused by the malaria parasite Plasmodium falciparum. The precise mechanisms underlying cerebral malaria pathogenesis are not entirely understood. To investigate the pathogenesis of cerebral malaria, we examined Plasmodium berghei ANKA (PbA) infection of C57Bl/6 mice, a well-established animal model of experimental cerebral malaria (ECM). We used intravital microscopy to image the brains in live mice undergoing malarial infection. We injected CB57Bl/6 mice with malaria-specific PbT-I CD8+ T cells or malaria-specific PbT-II CD4+ T cells a day before infection with PbA blood-stage parasites. Two-photon laser scanning microscopy was performed through a cover-slipped cranial window, which allowed observation of the immune response in real time. CB57Bl/6 mice infected with PbA showed symptoms of cerebral malaria 6-7 days after infection. PbT-I and PbT-II T cells were both present in the brain blood vessels from day 6 post-infection and entered the brain parenchyma by day 7. Flow cytometric analysis after intravascular Ab labelling confirmed the accumulation of transgenic T cells as well as endogenous CD4+ and CD8+ T cells within the brain parenchyma of both acutely infected and long-term cured mice. The presence of PbT-I T cells in the brain of cured mice was also confirmed by intravital microscopy. These results suggest that both CD4+ and CD8+ T cells infiltrate the brain during ECM, with some cells forming long-term memory in this site. They also raise the possibility that infiltration of CD4+ T cells into the brain parenchyma may contribute to cerebral immunopathology.