p-Nitrophenyl 2-O-methyl-,3-~-galactopyranoside and p-nitrophenyl 2-O-methyl-a-~-mannopyranoside were synthesized and their cleavage reactions were compared with those of p-nitrophenyl @-D-galactopyranoside and p-nitrophenyl a-D-mannopyranoside. The cleavage rates (35-55 ") and products formed from these glycosides (all capable (of a tram-diaxial orientation a t C-1 and C-2) in methanolic and aqueous base solution were studied. Reaction of the glycosides in methanolic sodium methoxide resulted in over-all retention of configuration, whereas the 2-0-met:hylglycosides gave substantial amounts of p-nitroanisole and its reduction products (formed by secondary reaction with 2-0-methyl sugar). Kinetic studies included the effect of base concentration, the hydrogen isotope effect, ionic strength effects, and the effect of hydrogen peroxide. Blocking of the C-2 oxygen by a methyl group caused an enormous decrease in the rate of cleavage and a change in reaction pathway in both cases. The pnitrophenyl glycosides react by neighboring-group participation of the C-2 oxyanion, whereas the 2-0-methylglycoside reactions proceed, a t least in methanolic sodium methoxide, by bimolecular nucleophilic aromatic substitution.