P. falciparum is the cause of the lethal form of malaria which results in thousands of deaths each year. The primary cause of death, cerebral malaria, is associated with the sequestration of erythrocytes infected with the mature stages of P. falciparum (trophozoites and schizonts) in the post capillary venules of the brain. The identification of the parasite protein(s) involved in this process will provide important vaccine candidate molecules and knowledge about the pathological processes involved in cell-cell adhesion in general. The mechanism of cytoadherence is studied in vitro using cultured lines of P. falciparum which bind to umbilical vein endothelial cells and C32 amelanotic melanoma cells. Mature stages of the parasite may induce knob-like protrusions in the erythrocyte membrane, and it was previously thought that ‘knobs’ were necessary although not sufficient for cytoadherence to occur both in vitro and during natural infection. We have derived a clone of the Brazilian isolate of P. falciparum, ITG2F6, and selected for cytoadherence by repeated passage over amelanotic melanoma cells. Chromosome analysis using pulsed-field gradient electrophoresis and DNA amplification using the polymerase chain reaction reveal that this clone has deleted the gene coding for knobs. Furthermore, cytoadherence which is independent of knobs occurs via the receptor for the platelet protein, thrombospondin.