To identify the molecules involved in the adhesion of Entamoeba histolytica trophozoites to target cells we used monoclonal antibodies (MAbs) and adhesion-deficient mutants. Human red blood cells (RBCs) were also used as specific carriers to identify the ameba molecules with affinity to the target cell receptors. MAbs Adh-1 and Adh-2 inhibited adhesion of RBCs to the trophozoites and recognized a 112-kDa surface protein that was present in the wild type strain, but was absent or modified in adhesion-deficient mutants. In other experiments, live trophozoites were incubated with fixed-RBCs and after lysis of the trophozoites, proteins attached to the RBCs surface were separated by PAGE, electrotransferred to nitrocellulose membranes and detected by polyclonal antibodies. The 112 kDa protein was found attached to the RBCs. Other molecules identified as proteins involved in the target cell-parasite contact were the 210, 160, 90, 70, 50 and 24 kDa proteins. The 112, 90 and 24 kDa polypeptides were functionally altered in adhesion-deficient mutants.