The hydrolyses of alpha- and beta-glucopyranosyl fluorides at near-neutral pH have been studied. The water (buffer-independent) reactions were characterized by values of Delta H-double dagger of 96 +/- 4 and 88 +/- 5 kJ mol(-1) and of Delta S-double dagger of -37 +- 12 and -38 +/- 17 J mol(-1) K-(1), respectively, and by multiple kinetic isotope effects measured by the isotopic quasi-racemate method. These effects, expressed as k(light)/k(heavy) for the alpha-fluoride at 80 degrees C and the beta-fluoride at 50 degrees C, were, respectively, for alpha D (C1), 1.14(2) and 1.08(6), for beta D (C2), 1.06(5) and 1.03(0), for ring O-18, 0.98(4) and 0.98(5), and for anomeric C-13, 1.03(2) and 1.01(7); a gamma D (C5) effect of 0.98(0) was also measured for the alpha-compound. A transition-state structure for the hydrolysis of the alpha fluoride, involving the ring in a flattened C-4(1) chair conformation, and an "exploded" S(N)2 disposition of water and fluoride ion about the anomeric center were located from BEBOVIB-IV and the initial structure, parameter settings, and procedure used by Tanaka et al. (Tanaka, Y.; Tao, A.; Blanchard, J. S.; Hehre, E. J. J. Biol. Chem. under review) in their study of the glucoamylase-catalyzed hydrolysis of this compound. The effects for the beta-fluoride are consistent with a more S(N)1-like transition state in which the sugar ring is again in a flattened C-4(1) conformation. In the presence of 2.0 M sodium azide; when the reaction of the alpha-fluoride becomes a classic S(N)2 reaction (Banait, N. S.; Jencks, W. P. J. Am. Chem. Sec. 1991, 113, 7951), the C-13 effect increases to 1.08(5) but the alpha D effect also increases modestly (to 1.16(9)). The reaction of the beta-fluoride in 0.3 M succinate buffer is largely (formally) a bimolecular reaction of the acidic form of the buffer; effects are as follows : alpha D, 1.11(0); beta D, 1.05(9); gamma D, 0.98(1); ring O-18, 0.98(8); anomeric C-13, 1.06(4). The apparent promotion of A(N)D(N) reactions of the beta-fluoride by succinate monoanion rather than dianion suggests that the microscopic reaction is the catalysis by neutral succinic acid of the formation of 1,2-anhydroglucose from the monoanion of the glucosyl fluoride.