The acidity constants of adenosine-5′-mono- and diphosphate (AMP and ADP) were determined at 25.00±0.1°C by potentiometric titration in pure water and different solvent mixtures (methanol, ethanol, N,N-dimethylformamide, dimethylsulfoxide, acetone, and dioxane). The ionization of AMP and ADP depends on both the proportion and the nature of the organic solvent used. The pKa1 values for both AMP and ADP are slightly influenced as the solvent is enriched in ethanol and methanol and remains practically constant in presence of different amounts of DMF and DMSO. A pronounced change in the pKa1 values is observed as the solvent is enriched in acetone or dioxane. It is concluded that the electrostatic effect has only a relatively small influence on the dissociation equilibrium, whereas other solvent effects such as solvent basicity, hydrogen bonding and protonsolvent interactions play an important role. © 1994 Springer-Verlag.