The effect of conformation on glycoside reactivity was investigated by studying the hydrolysis of a selection of 3,6-anhydroglucosides as models for glucose in the highly reactive C-1(4) conformation. Methyl 3,6-anhydro-beta-D-glucopyranoside was found to hydrolyze 200-400 times faster than methyl glucosides in the C-4(1) conformation, while methyl 3,6-anhydro-beta-D-galactopyranoside, which is in the B-1,B-4 conformation, was less reactive than methyl beta-D-galactopyranoside. Methyl (3,6-anhydro-beta-D-glucopyranosyl)-(1-->6)-alpha-D-glucopyranoside, methyl (3,6-anhydro-alpha-D-glucopyranosyl)-(1-->6)-alpha-D-glucopyranosyl-(1-->6)-alpha-D-glucopyranoside, and methyl (3,6-anhydro-alpha-D-glucopyranosyl)-(1-->6)-alpha-D-glucopyranosyl-(1-->6)-alpha-D-glucopyranoside were prepared and found to react selectively at the anhydro residue. The finding that C-1(4) conformers of glucosides are highly reactive species is in accordance with and supports previous results showing that axial OH groups are less electron withdrawing than equatorial OH groups.