A primary infection of mice with Plasmodium chabaudi chabaudi (AS) is characterized by a rapid and marked inflammatory response. Typically, IL-12, TNF-alpha and IFN-gamma are produced in the spleen, and are transiently present in plasma. The cells involved in this early response are unknown. Here we show that dendritic cells derived from GM-CSF-stimulated mouse bone marrow cultures produce TNF-alpha within 30 min of exposure to P.c.chabaudi schizonts. IL-6, IL-12p40 and p70 follow this. The production of these cytokines was not dependent on the presence of T cells or NK cells and did not require CD40. Incubation of dendritic cells with P.c.chabaudi schizonts also resulted in up-regulation of MHC class II, CD40 and CD86 but not CD80. In contrast to some strains of the human parasite, P. falciparum, P.c. chabaudi (AS) did not inhibit the up-regulation of MHC class II, CD86 or CD40 induced by LPS. Therefore, the erythrocytic stages of P.c.chabaudi are able to activate dendritic cells directly. The consequences of such an interaction could be rapid activation of TH1 cells and induction of immunity, and in the event of a large response also induction of TNF-alpha associated pathology.