Solvolysis rates for trialkylammonium and tetraalkylammonium salts of ADPβS at 25°C and ADP at 80°C in water, N,N-dimethylformamide (DMF) and water-DMF mixtures are reported. ADPβS undergoes solvolysis much faster than ADP under all conditions. The solvolysis of tris-triethylammonium ADPβS is 40-fold faster in DMF than in water at 25°C, but the solvolysis of tris-tetramethylammonium ADPβS is only slightly faster in DMF than in water. The solvolysis rate for tris-tetramethylammonium ADPβS increases whereas that for tris-triethylammonium ADPβS decreases upon addition of small percentage of H2O to DMF. The corresponding salts of ADP do not undergo detectable solvolysis at 25°C, but react at 80°C, where the trialkylammonium and tetraalkylammonium salts exhibit analogous but much smaller effects on solvolysis rates. The results indicate the operation of two effects of DMF in enhancing the solvolysis of ADPβS: (a) DMF decreases the acid dissociation constant of ADPβS, which leads to an increased fraction being in the solvolytically labile dianionic form. (b) The decreased polarity of DMF relative to water enhances the rate by a medium effect of destabilizing the ground state relative to the transition state in a dissociative mechanism. Comparisons of the solvolytic rates for ADPβS relative to ADP suggest that the two react by different mechanism, ADP by a SN2 mechanism via a dissociative transition state and ADPβS by a purely dissociative mechanism via a discrete thiometaphosphate monoanion as an intermediate.