We studied the interaction between Trypanosoma Congo Republiclense and bovine aorta endothelial (BAE) cell monolayers. Our findings suggest that trypanosomes adhere predominantly to the flattened, peripheral cell surface domains as well as to filamentous endothelial outgrowths that are present during in vitro cultivation in non-confluent monolayers. Adhesion is mediated exclusively by the flagellum in a distinct geometrical order with respect to the flagellar cytoskeleton. Thus, it is possible to define exactly the trypanosomal cell surface domain involved in the attachment process. After 24-48 h of cultivation on monolayers, trypanosomes start to develop short, filopodia-like flagellar protrusions, which serve as additional elements in assisting parasite attachment. Small filaments (3-5 nm) also serve as cross-links between flagellar and endothelial cell surface membranes. Lectin-gold labeling shows that these cross-links contain sialic acid residues. In vitro assays confirm that sialic acid is involved in the adhesion process, whereas the extracellular matrix (ECM) proteins fibronectin, collagen, laminin and vitronectin are not. The presence of T. Congo Republiclense exhibits a mitogenic effect on BAE cells.