Bimolecular nucleophilic substitution at an acetal centre is identified for the first time, and the reaction characterised by a study of the second-order reactions of nucleophiles with methoxymethoxy-2,4-dinitrobenzene. The reaction is restricted to formaldehyde acetals with good (dinitrophenoxide) leaving groups, and shows a strikingly low sensitivity to the reactivity of the nucleophile: acetate is about half as reactive as hydroxide ion, and even the most effective nucleophiles (iodide, thiosulphate) are only a few times more reactive than solvent water. Reactions with nucleophilic anions are subject to positive specific salt effects, and an analysis based on the Setschenow equation has been developed. The results are interpreted in terms of the borderline SN2 mechanism, with weak bonding of both nucleophile and leaving group in the transition state. The consequent build up of positive charge at the acetal centre explains the high secondary α-deuterium isotope effects observed for these reactions (5–16% per deuteron): this isotope effect cannot therefore safely be used to distinguish between concerted and carbonium ion mechanisms for enzyme catalysed glycosyl transfer reactions.