OBJECTIVE To approve a theoretical basis for the molecular pathogenesis of human cerebral malaria and treatment with prevention. METHODS The blood samples were collected from 24 patients with cerebral malaria, 143 with falciparum malaria, 34 with vivax malaria and 20 healthy controls from the endemic areas of Yunnan Province, China. Using the sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) technique, we determined the molecular mass (Mr) of these Plasmodium falciparum (P. falciparum) erythrocyte membrane protein 1 (PfEMP1) molecules. RESULTS Our findings indicate that higher molecular mass (260 kDa-320 kDa) forms of PfEMP1 were expressed on parasitized erythrocyte (PE) from human cerebral malaria patients. Compared with PfEMP1 expressed on PE from human cerebral malaria patients, the expression of PfEMP1 and Plasmodium vivax (P. vivax) erythrocyte membrane protein 1 (PvEMP1) on PE from falciparum malaria patients and vivax malaria patients did not have multiple bands of PfEMP1 of > or = 260 kDa, but had a PfEMP1 with molecular mass of 240 kDa and a PvEMP1 with molecular mass of 180 kDa band separately. Healthy controls expressed an EMP of molecular mass of 140 kDa. CONCLUSIONS Results confirm the antigenic variation of higher molecular mass of PfEMP1 whose molecular mass is equal to or exceeds 260 kDa-320 kDa on PE of patients with cerebral malaria. Our results show that the binding of large antigenic variability PfEMP1 molecular mass of 260 kDa-320 kDa on PE from human cerebral malaria patients with diverse receptor molecules on the endothelial cell (EC) of the cerebral microvessels may be involved in the molecular pathogenesis of cerebral malaria.