Plasmodium falciparummalaria in humans and animal models of this disease have revealed changes in the infected host that are consistent with a systemic inflammatory response. Although it has been proposed that endothelial cell adhesion molecules (CAM) contribute to the adhesive interactions of Plasmodium-infected erythrocytes and immune cells with vascular endothelial cells, ECAM expression has not been systematically studied in Plasmodium-infected animals. In this study, the dual radiolabeled monoclonal antibody method was used to quantify the expression of different ECAMs (ICAM-1, VCAM-1, P-selectin, E-selectin) in different regional vascular beds of Plasmodium bergheiANKA-inffected mice (PbA), a well-recognized model of human cerebral malaria. The roles of T lymphocytes and certain cytokines (TNF-α, IL-12, IFN-γ) in mediating the infection-induced expression of ICAM-1 and P-selectin were assessed by using relevant mutant mice. Wild-type (WT) mice exhibited highly significant increases in the expression of ICAM-1, VCAM-1, and P-selectin (but not E-selectin) in all vascular beds on the 6th day of PbAinfection. The PbA-induced upregulation of ICAM-1 was significantly blunted in mice that were either deficient in IFN-α, IL-12 (but not TNF1b) or T lymphocytes (Rag-1 deficiency); however, these responses were tissue specific. These findings indicate that vascular endothelial cells in most regional circulations assume an inflammatory phenotype and that cytokines and immune cells mediate this response in a tissue-specific manner. Microcirculation(2002) 9, 463–470. doi:10.1038/sj.mn.7800159