Nucleophile C-11/C-14 [k(11)/k(14)] and secondary alpha-deuterium [(k(H)/k(D))(alpha)] kinetic isotope effects (KIEs) were measured for the S(N)2 reactions between tetrabutylammonium cyanide and ethyl iodide, bromide, chloride, and tosylate in anhydrous DMSO at 20 degrees C to determine whether these isotope effects can be used to determine the structure of S(N)2 transition states. Interpreting the experimental KIEs in the usual fashion (i.e., that a smaller nucleophile KIE indicates the Nu-C-alpha transition state bond is shorter and a smaller (k(H)/k(D))(alpha) is found when the Nu-LG distance in the transition state is shorter) suggests that the transition state is tighter with a slightly shorter NC-C-alpha, bond and a much shorter C-alpha-LG bond when the substrate has a poorer halogen leaving group. Theoretical calculations at the B3LYP/aug-cc-pVDZ level of theory support this conclusion. The results show that the experimental nucleophile C-11/C-14 KIEs can be used to determine transition-state structure in different reactions and that the usual method of interpreting these KIEs is correct. The magnitude of the experimental secondary alpha-deuterium KIE is related to the nucleophile-leaving group distance in the S(N)2 transition state (R-TS) for reactions with a halogen leaving group. Unfortunately, the calculated and experimental (k(H)/k(D))(alpha)'s change oppositely with leaving group ability. However, the calculated (k(H)/k(D))(alpha)'s duplicate both the trend in the KIE with leaving group ability and the magnitude of the (k(H)/k(D))(alpha)'s for the ethyl halide reactions when different scale factors are used for the high and the low energy vibrations. This suggests it is critical that different scaling factors for the low and high energy vibrations be used if one wishes to duplicate experimental (k(H)/k(D))(alpha)'s. Finally, neither the experimental nor the theoretical secondary alpha-deuterium KIEs for the ethyl tosylate reaction fit the trend found for the reactions with a halogen leaving group. This presumably is found because of the bulky (sterically hindered) leaving group in the tosylate reaction. From every prospective, the tosylate reaction is too different from the halogen reactions to be compared.