Host-pathogen interactions and macromolecular complex formation during Apicomplexa parasite invasion of their host cells represents an important action target for designing methods for controlling these microorganisms. Knowledge regarding the biology and functions of proteins and interactions occurring dining invasion is scarce regarding Plasmodium vivax due to the difficulty of propagating the parasite in vitro. This study was thus aimed at evaluating P. vivax RON-2, -4 and AMA-1 proteins, bearing in mind then capability for niteracting with human reticulocytes. An attempt was also made to ascertain whether binary interactions between R0N2. -4. -5 and AMA-1 proteins could be associated with a protein complex, as has been suggested for P. falciparum. Concerning receptor-ligand interactions, it was found that PiAMA-DI-II. PvR0N2-RI. PvR0N2-RII and P1R0N4 fragments bound to CD71+ reticulocytes. It was particularly interesting to find that Pi AMA-1 domain I contained a 20 residue-long region responsible for specific, high affinity interaction with CD71+reticulocyte receptors. ELISA revealed relevant interactions between the rPvAMA-DII-III fragment and iPi RON2-RI. rPiRON2-RII and rPrRON4 and between rPi RON5 and Pi RON 2 fragments. These results represent an advance regaiding knowledge concerning P. vivax biology and suggest the participation of some of these proteins’ regions in host-pathogen and protein-protein interactions which might be essential regarding the search for specific control methods against this parasite species.