Successful invasion of mammalian cells by pathogenic parasites is generally considered, from circumstantial evidence, to be a consequence of specific mechanisms of recognition of cell surface components--this has stimulated investigations of the biochemical characterization of such molecules. Several studied of trypanosomiasis have examined the ability of parasites to interact with mammalian cells. However, knowledge of the mammalian cell surface 'receptors' which interact with the parasite is limited. We now report that fibronectin, which is a high molecular weight glycoprotein present in blood, connective tissue and at cell surfaces, binds specifically to Trypanosoma cruzi trypomastigotes. The reaction is specific, reversible (in the presence of a 100-fold molar excess of unlabelled ligand) and of moderate affinity (Kd = 11.36 nM). Various other proteins (for example, thyroglobulin, ferritin, catalase, aldolase, human IgG and bovine serum albumin) had no significant effect on the binding of labelled ligand to the parasite surface. Addition of anti-fibronectin antibodies to the culture medium significantly inhibited the infection of rat fibroblasts (3T3 FR) by T. cruzi trypomastigotes, suggesting that cell surface fibronectin may act as a recognition site for attachment of the parasites.