The ability of the surface galactose (Gal)/N-acetyl-D-galactosamine (GalNAc) receptor of mouse peritoneal macrophages to recognize bloodstream trypomastigotes of Trypanosoma cruzi was examined. The parasite's uptake is improved by its desialylation and impaired by its treatment with Gal or GalNAc-binding lectins. Further incubation of asialoparasites with lectins for Gal-blockage (PNA and RCA I) reverses, in a dose-dependent way, 35-80% of the neuraminidase effect on the endocytosis of T. cruzi. Similar effects were observed when lectins for GalNAc-blockage (PHA, WPA and DBA) were used. Asialoerythrocytes or galactosyl-oligosaccharides added during the parasite-cell interaction assays, also competed with the normal or desialylated tryptomastigotes for receptors on the host cell surface, inhibiting their uptake and reversing the effect of neuraminidase. Although indirect, these results are strongly suggestive that the Gal/GalNAc recognition system of the macrophages is involved in the interiorization of T. cruzi.