Cerebral malaria (CM) is a serious complication of Plasmodium falciparum infection, causing significant morbidity and mortality among young children and nonimmune adults in the developing world. Although previous work on experimental CM has identified T cells as key mediators of pathology, the APCs and subsets therein required to initiate immunopathology remain unknown. In this study, we show that conventional dendritic cells but not plasmacytoid dendritic cells are required for the induction of malaria parasite-specific CD4(+) T cell responses and subsequent experimental CM. These data have important implications for the development of malaria vaccines and the therapeutic management of CM. The Journal of Immunology, 2007, 178: 6033-6037.