Some strains of Plasmodium falciparum form erythrocyte rosettes that are believed to result from a lectin interaction between malaria-infected and uninfected erythrocytes. The sulfated glycoconjugate heparin and certain heparin derivatives have been observed to disrupt rosettes. To investigate this interaction further, we have studied the effects of four sulfated glycoconjugates on 15 fresh isolates of P. falciparum from Papua New Guinea. A broader range of sulfated glycoconjugates has been tested against a laboratory strain. A concentration of 1,000 µg/ml of dextran sulfate (molecular weight [MW] 500,000) was the most potent disrupter of rosettes. Fucoidan, heparin, and dextran sulfate (MW 5,000) were of decreasing effectiveness in 14 of 15 fresh isolates. The same relationship was true for the laboratory strain. Pentosan polysulfate and sulfatide also disrupted rosettes; chondroitin sulfates A, B, and C and keratan sulfate gave either minimal or no rosette disruption. Thus, some sulfated glycoconjugates are potent disrupters of P. falciparum erythrocyte rosettes. Sulfated glycoconjugates that are potent disrupters of P. falciparum rosettes may prove useful in identifying ligands involved in rosette formation.