Previous studies have shown that adhesion to fibroblastic cells of cell culture-derived trypomastigotes of Trypanosoma cruzi probably occurs through a ligand-receptor interaction. The results now obtained indicate that solubilization with a mild detergent ('Chaps', 0.8%) of 125I-surface proteins of trypomastigotes, followed by detergent removal and interaction of the solubilized proteins with a monolayer of intact Vero cells, brings about binding to the cells of a parasite surface protein, which exhibits a molecular weight of 83,000 and isoelectric point of 8.1-8.6 upon two-dimensional polyacrylamide gel electrophoresis. This polypeptide was detected in extracts of highly adherent, extracellularly incubated parasites, but not in extracts of poorly adhesive, recently released trypomastigotes. The detergent-free extracts of incubated trypomastigotes inhibit attachment of live parasites to Vero cells, while extracts of fresh trypomastigotes are nearly ineffective. Binding of the parasite polypeptide to the cells is stimulated by parasite trypsinization or activation in the presence of tunicamycin, and it is inhibited by the presence of mannan or by Vero cell trypsinization, thus showing a similar behaviour to that observed for parasite attachment to Vero cells under these conditions. These results suggest that the surface membranes of activated, highly adherent T. cruzi trypomastigotes contain an 83 kDa polypeptide which acts as a lectin-like protein that can interact with the surface of Vero fibroblasts, probably through mannose residues of a glycoprotein receptor of the host cell.