Syntheses of the methyl glycosides of the Lewis b {α- l-Fuc-(1→2)-β- d-Gal-(1→3)[α- l-Fuc-(1→4)]-β- d-GlcNAc-} and Y {α- l-Fuc-(1→2)-β- d-Gal-(1→4)[α- l-Fuc-(1→3)]-β- d-GlcNAc-} human blood-group determinants and both their 6a-deoxy and N-deacetylated derivatives are reported. In the case of the Lewis b structure (Le b-OMe), the 6a- O-mesyl and 6a-deoxy-6a-iodo derivatives were also prepared. The conformational preferences predicted by HSEA calculation are shown to be in good agreement with expectations based on 1H- and 13C-n.m.r. spectroscopy. The immunochemical data based on inhibition and thermodynamic studies require that the binding of Le b-OMe and Y-OMe by the lectin IV of Griffonia simplicifolia does not involve recognition of the OMe, NHAc, or 6a-OH group and, consequently, occurs at a cleft at the surface of the protein. The complex formed between the lectin and 6a-deoxy-6a-iodo-Le b-OMe provided the heavy nuclei required for the solution of the X-ray crystal structure.