Cytoadherence of Plasmodium falciparum-infected erythrocytes to melanoma cells was analysed using strains or isolates of parasites expressing or not expressing knobs (K+ or K− phenotype) on the erythrocyte surface. Both K+ and K− parasites had the capacity to cytoadhere to melanoma cells. Using a panel of melanoma cell lines with different surface expression of the cytoadherence receptors CD36, thrombospondin and ICAM-1 indicated that CD36 was the major receptor for parasites of both K+ and K− phenotypes. Binding competition experiments between K+ and K−-infected erythrocytes suggested that K+ cytoadherence is of higher affinity than that of K− parasites. However, some K− cytoadherence was also found in isolates containing mixed populations of K+ and K− parasites. The interaction of the two types of infected erythrocytes with melanoma cells also differed ultrastructurally, erythrocytes of K+ phenotype showing intimate interdigitations with microvilli on the melanoma cells, while erythrocytes of K− phenotype displayed more separated interactions with fewer sites of contact and involving only a few melanoma cell microvilli. One and the same infected erythrocyte may co-express the ligand for CD36-mediated cytoadherence and the structures mediating binding of uninfected erythrocytes to form rosettes.